当前期刊: Journal of Human Genetics Go to current issue    加入关注   
显示样式:        排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Identification of new mutations in patients with hereditary spherocytosis by next-generation sequencing
    J. Hum. Genet. (IF 3.545) Pub Date : 2020-01-24
    Li Qin; Yanbo Nie; Hong Zhang; Long Chen; Donglei Zhang; Yani Lin; Kun Ru
    更新日期:2020-01-24
  • Association of the IL16 Asn1147Lys polymorphism with intravenous immunoglobulin resistance in Kawasaki disease
    J. Hum. Genet. (IF 3.545) Pub Date : 2020-01-22
    Hea-Ji Kim; Jae-Jung Kim; Sin Weon Yun; Jeong Jin Yu; Kyung Lim Yoon; Kyung-Yil Lee; Hong-Ryang Kil; Gi Beom Kim; Myung-Ki Han; Min Seob Song; Hyoung Doo Lee; Kee Soo Ha; Young Mi Hong; Gi Young Jang; Jong-Keuk Lee

    Kawasaki disease (KD) is an acute, self-limited vasculitis, mainly affecting children younger than 5 years old, with accompanying fever and signs of mucocutaneous inflammation. Intravenous immunoglobulin (IVIG) is the standard treatment for KD; however, ~15% of patients are resistant to IVIG treatment. To identify protein coding genetic variants influencing IVIG resistance, we re-analyzed our previous genome-wide association study (GWAS) data from 296 patients with KD, including 101 IVIG non-responders and 195 IVIG responders. Five nonsynonymous SNPs (nsSNPs) in five immune-related genes, including a previously reported SAMD9L nsSNP (rs10488532; p.Val266Ile), were associated with IVIG non-response (odds ratio [OR] = 1.89–3.46, P = 0.0109–0.0035). In a replication study of the four newly-identified nsSNPs, only one in the interleukin 16 (IL16) gene (rs11556218, p.Asn1147Lys) showed a trend of association with IVIG non-response (OR = 1.54, P = 0.0078). The same IL16 nsSNP was more significantly associated with IVIG non-response in combined analysis of all data (OR = 1.64, P = 1.25 × 10−4). Furthermore, risk allele combination of the IL16 CT and SAMD9L TT nsSNP genotypes exhibited a very strong effect size (OR = 9.19, P = 3.63 × 10−4). These results implicate IL16 as involved in the mechanism of IVIG resistance in KD.

    更新日期:2020-01-22
  • 更新日期:2020-01-22
  • Molecular mechanisms determining severity in patients with Pierson syndrome
    J. Hum. Genet. (IF 3.545) Pub Date : 2020-01-21
    Shogo Minamikawa; Saori Miwa; Tetsuji Inagaki; Kei Nishiyama; Hiroshi Kaito; Takeshi Ninchoji; Tomohiko Yamamura; China Nagano; Nana Sakakibara; Shingo Ishimori; Shigeo Hara; Norishige Yoshikawa; Daishi Hirano; Ryoko Harada; Riku Hamada; Natsuki Matsunoshita; Michio Nagata; Yuko Shima; Koichi Nakanishi; Hiroaki Nagase; Hiroki Takeda; Naoya Morisada; Kazumoto Iijima; Kandai Nozu
    更新日期:2020-01-21
  • Genome-wide meta-analysis associates GPSM1 with type 2 diabetes, a plausible gene involved in skeletal muscle function
    J. Hum. Genet. (IF 3.545) Pub Date : 2020-01-21
    Qiuju Ding; Amelia Li Min Tan; E. J. Parra; Miguel Cruz; Xueling Sim; Yik-Ying Teo; Jirong Long; Habiba Alsafar; Enrico Petretto; E-Shyong Tai; Huimei Chen
    更新日期:2020-01-21
  • Genetic screening for potassium channel mutations in Japanese autosomal dominant spinocerebellar ataxia
    J. Hum. Genet. (IF 3.545) Pub Date : 2020-01-07
    Yui Tada; Kodai Kume; Yukiko Matsuda; Takashi Kurashige; Yuhei Kanaya; Ryosuke Ohsawa; Hiroyuki Morino; Hayato Tabu; Satoshi Kaneko; Toshihiko Suenaga; Akira Kakizuka; Hideshi Kawakami
    更新日期:2020-01-07
  • Genetic polymorphisms in the opioid receptor delta 1 ( OPRD1) gene are associated with methadone dose in methadone maintenance treatment for heroin dependence
    J. Hum. Genet. (IF 3.545) Pub Date : 2020-01-07
    Chiu-Ping Fang; Sheng-Chang Wang; Hsiao-Hui Tsou; Ren-Hua Chung; Ya-Ting Hsu; Shu Chih Liu; Hsiang-Wei Kuo; Tung-Hsia Liu; Andrew C. H. Chen; Yu-Li Liu

    Delta opioid receptor (DOR) is well known to be involved in heroin dependence. This study tested the hypothesis that single nucleotide polymorphisms (SNPs) in the opioid receptor delta 1 (OPRD1) gene coding region are associated with treatment responses in a methadone maintenance therapy (MMT) cohort in Taiwan. Three hundred forty-four MMT patients were recruited. Diastolic/systolic blood pressure, heart rate, methadone dosage, and plasma concentrations of methadone were recorded. Twenty-five SNPs located within the OPRD1 genetic region were selected and genotyped from the genomic DNA of all 344 participants. After pairwise tagger analyses, tagger SNP rs204047 showed a significant association with methadone dosage (P = 0.0019), and tagger SNPs rs204047 and rs797397 were significantly associated with plasma R, S-methadone concentrations (P < 0.0006) in patients tested negative in the urine morphine test, which indicated patients with a better response to MMT. The major genotype carriers showed a higher methadone dosage and higher plasma concentrations of R, S-methadone than the minor genotype carriers. The results indicated that OPRD1 genetic variants were associated with methadone dosage and methadone plasma concentration in MMT patients with a negative morphine test result.

    更新日期:2020-01-07
  • Identification of a CDH12 potential candidate genetic variant for an autosomal dominant form of transgrediens and progrediens palmoplantar keratoderma in a Tunisian family
    J. Hum. Genet. (IF 3.545) Pub Date : 2020-01-07
    Cherine Charfeddine; Hamza Dallali; Ghaith Abdessalem; Kais Ghedira; Yosr Hamdi; Sahar Elouej; Zied Landoulsi; Valérie Delague; Arnaud Lagarde; Nicolas Levy; Aziz El-Amraoui; Mohamed Samir Boubaker; Sonia Abdelhak; Mourad Mokni
    更新日期:2020-01-07
  • 更新日期:2020-01-07
  • Impact of proactive high-throughput functional assay data on BRCA1 variant interpretation in 3684 patients with breast or ovarian cancer
    J. Hum. Genet. (IF 3.545) Pub Date : 2020-01-06
    Hyun-Ki Kim; Eun Jin Lee; Young-Jae Lee; Jisun Kim; Yongsub Kim; Kyunggon Kim; Shin-Wha Lee; Suhwan Chang; Young Joo Lee; Jong Won Lee; Woochang Lee; Sail Chun; Byung Ho Son; Kyung Hae Jung; Yong-Man Kim; Won-Ki Min; Sei-Hyun Ahn
    更新日期:2020-01-06
  • Mutations in TOMM70 lead to multi-OXPHOS deficiencies and cause severe anemia, lactic acidosis, and developmental delay
    J. Hum. Genet. (IF 3.545) Pub Date : 2020-01-06
    Xiujuan Wei; Miaomiao Du; Jie Xie; Ting Luo; Yan Zhou; Kun Zhang; Jin Li; Deyu Chen; Pu Xu; Manli Jia; Huaibin Zhou; Hezhi Fang; Jianxin Lyu; Yanling Yang
    更新日期:2020-01-06
  • A proposal on the first Japanese practical guidance for the return of individual genomic results in research settings
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-23
    Yayoi Aizawa; Fuji Nagami; Noriko Ohashi; Kazuto Kato
    更新日期:2019-12-23
  • Variant in ERAP1 promoter region is associated with low expression in a patient with a Behçet-like MHC-I-opathy
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-23
    Chrysoula Dimopoulou; Jens D. Lundgren; Jon Sundal; Henrik Ullum; Pål Aukrust; Finn C. Nielsen; Rasmus L. Marvig
    更新日期:2019-12-23
  • Association of ALPL variants with serum alkaline phosphatase and bone traits in the general Japanese population: The Nagahama Study
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-20
    Miho Nagata; Kazuya Setoh; Meiko Takahashi; Koichiro Higasa; Takahisa Kawaguchi; Hidenori Kawasaki; Takahito Wada; Atsushi Watanabe; Hideaki Sawai; Yasuharu Tabara; Takahiro Yamada; Fumihiko Matsuda; Shinji Kosugi
    更新日期:2019-12-20
  • Genotyping of Malaysian G6PD-deficient neonates by reverse dot blot flow-through hybridisation
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-20
    M. F. Alina; R. Z. Azma; J. Norunaluwar; I. Azlin; A. J. Darnina; F. C. Cheah; A. R. Noor-Farisah; A. A. Siti-Hawa; X. R. K. Danny; Noor-Fadzilah Zulkifli; O. Ainoon
    更新日期:2019-12-20
  • Evaluating the predictive value of genetic risk score in colorectal cancer among Chinese Han population
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-19
    Ding Ye; Danjie Jiang; Simeng Gu; Yingying Mao; Sangni Qian; Shujuan Lin; Qilong Li; Jinhua Yang; Kunhong Zhong; Mingjuan Jin; Kun Chen
    更新日期:2019-12-19
  • Identification of susceptibility locus shared by IgA nephropathy and inflammatory bowel disease in a Chinese Han population
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-19
    Dianchun Shi; Zhong Zhong; Meng Wang; Lu Cai; Dongying Fu; Yuan Peng; Lin Guo; Haiping Mao; Xueqing Yu; Ming Li
    更新日期:2019-12-19
  • Identification of novel pathogenic copy number variations in Charcot-Marie-Tooth disease
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-18
    J. Mortreux; J. Bacquet; A. Boyer; E. Alazard; R. Bellance; A. G. Giguet-Valard; M. Cerino; M. Krahn; F. Audic; B. Chabrol; V. Laugel; J. P. Desvignes; C. Béroud; K. Nguyen; A. Verschueren; N. Lévy; S. Attarian; V. Delague; C. Missirian; N. Bonello-Palot
    更新日期:2019-12-19
  • A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-12
    Leigh A. M. Demain; Erica. H. Gerkes; Richard J. H. Smith; Leslie P. Molina-Ramirez; Raymond T. O’Keefe; William G. Newman
    更新日期:2019-12-13
  • Exome sequencing identifies de novo splicing variant in XRCC6 in sporadic case of autism
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-12
    Calvin P. Sjaarda; Shalandra Wood; Amy J. M. McNaughton; Sarah Taylor; Melissa L. Hudson; Xudong Liu; Andrea Guerin; Muhammad Ayub
    更新日期:2019-12-13
  • The associations between three genome-wide risk variants for serum C-peptide of T1D and autoantibody-positive T1D risk, and clinical characteristics in Chinese population
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-12
    Yingjie Feng; Yuyue Zhang; Yang Chen; Shu Chen; Min Shen; Qi Fu; Yunqiang He; Yuwei Liu; Hsiang-Ting Hsu; Xinyu Xu; Heng Chen; Tao Yang; Kuanfeng Xu

    Aims Recent meta-genome-wide association studies identified several genetic variants associated with beta-cell function in type 1 diabetes (T1D). The aim of this study was to investigate the associations between these variants and T1D risk, C-peptide levels, islet-specific autoantibodies, and lipid levels in Chinese Han population. Methods A total of 1005 unrelated autoantibody-positive T1D cases and 1417 healthy controls were included, which were genotyped for rs559047, rs9260151, and rs3135002. T1D individuals were measured for both C-peptide and lipid levels. Logistic regression models were used to examine these associations. Results We found that rs3135002 A allele showed a genome-wide significant association with T1D risk (OR = 0.22, 95% CI = 0.17–0.30; P = 7.49 × 10−27), and significant heterogeneity of effect size was observed between early-onset and later-onset T1D subgroups (I2 = 80% and P = 0.026). Rs559047 had a nominal association with fasting C-peptide levels in newly diagnosed T1D individuals (P = 0.036). Moreover, rs3135002 A allele was significantly associated with GADA positivity (OR = 0.52, 95% CI = 0.30–0.91, P = 0.02). In addition, nominal correlations were observed with HDL levels for rs559047 (P = 0.042), while LDL levels for rs9260151 (P = 0.032) in T1D individuals. Conclusions Our results indicate that there are both similarities and differences for the associations of genetic variants among T1D development, progression, and related autoimmunity, metabolic traits.

    更新日期:2019-12-13
  • Identification of novel FBN1 variations implicated in congenital scoliosis
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-11
    Mao Lin, Sen Zhao, Gang Liu, Yingzhao Huang, Chenxi Yu, Yanxue Zhao, Lianlei Wang, Yuanqiang Zhang, Zihui Yan, Shengru Wang, Sen Liu, Jiaqi Liu, Yongyu Ye, Yaping Chen, Xu Yang, Bingdu Tong, Zheng Wang, Xinzhuang Yang, Yuchen Niu, Xiaoxin Li, Yipeng Wang, Jianzhong Su, Jian Yuan, Hengqiang Zhao, Shuyang Zhang, Guixing Qiu, Shiro Ikegawa, Jianguo Zhang, Zhihong Wu, Nan Wu
    更新日期:2019-12-11
  • Ambroxol improves skeletal and hematological manifestations on a child with Gaucher disease
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-11
    Wenjun Jiang, Mengni Yi, Gustavo H. B. Maegawa, Huiwen Zhang
    更新日期:2019-12-11
  • New evidence for associations between vitamin D receptor polymorphism and obesity: case-control and family-based studies
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-12-09
    Songcheng Yu, Xing Li, Fei Yu, Zhenxing Mao, Yan Wang, Yuan Xue, Hualei Sun, Yue Ba, Chongjian Wang, Wenjie Li
    更新日期:2019-12-09
  • Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-11-28
    Eungu Kang, Yoon-Myung Kim, Go Hun Seo, Arum Oh, Hee Mang Yoon, Young-Shin Ra, Eun Key Kim, Heyry Kim, Sun-Hee Heo, Gu-Hwan Kim, Mark J. Osborn, Jakub Tolar, Han-Wook Yoo, Beom Hee Lee
    更新日期:2019-11-28
  • Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype–phenotype relationships
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-11-26
    Carlos Rodríguez-Martín, Cristina Robledo, Gema Gómez-Mariano, Sara Monzón, Ana Sastre, Jose Abelairas, Constantino Sábado, Nieves Martín-Begué, Joan Carles Ferreres, Ana Fernández-Teijeiro, Ricardo González-Campora, María José Rios-Moreno, Ángel Zaballos, Isabel Cuesta, Beatriz Martínez-Delgado, Manuel Posada, Javier Alonso
    更新日期:2019-11-27
  • A novel POC1A variant in an alternatively spliced exon causes classic SOFT syndrome: clinical presentation of seven patients
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-11-26
    Adila Al-Kindi, Maryam Al-Shehhi, Ana Westenberger, Christian Beetz, Patrick Scott, Oliver Brandau, Lia Abbasi-Moheb, Zafer Yüksel, Peter Bauer, Arndt Rolfs, Nana-Maria Grüning

    Biallelic pathogenic variants in POC1A are ultra rare. They have been reported in 13 families as causing either Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis (SOFT) syndrome, or a milder partially overlapping phenotype, variant POC1A-related syndrome. This pleiotropic effect is likely precipitated by the variant’s location and respective affected protein domain. Here, we describe seven patients from two consanguineous Omani families with classic SOFT syndrome and a novel homozygous POC1A variant (c.64G>T; p.(Val22Phe)), which is the first one described for the alternative exon 2. This result refines the POC1A mutational spectrum relevant for exertion of the described pleiotropic effect. Furthermore, six of our patients experienced recurrent mild to severe respiratory difficulties that have not been previously reported for SOFT syndrome and may be an underdiagnosed or a genotype-specific complication that warrants attention in future studies. Thus, our study unravels new aspects of the genotype-phenotype correlation suggested by previous reports.

    更新日期:2019-11-26
  • Attitude and perceptions toward miscarriage: a survey of a general population in Japan
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-11-25
    Chihiro Banno, Mayumi Sugiura-Ogasawara, Takeshi Ebara, Shoko Ide, Tamao Kitaori, Takeshi Sato, Kiwamu Ando, Yoko Morita

    Miscarriage is the greatest complication of pregnancy, and 70–80% of early miscarriages are mostly due to chromosomal abnormalities in the embryo. There is no evidence that stress is a direct cause of miscarriage. Despite these findings, in a national US survey on the causes of miscarriage, many Americans mistakenly attributed miscarriage to the mental state or behavior of the women. We conducted a survey to assess public attitudes and perceptions regarding the cause and prevalence of miscarriage in Japan. We sent out a questionnaire consisting of 17 questions. The 5000 recipients consisted of men and women (1:1 ratio) aged 18–69 who resided in Aichi Prefecture. A total of 1257 recipients (25%) responded to the questionnaire and 1219 valid respondents (24%) were included in the analyses. Of these, 62% considered a genetic abnormality of the fetus as the cause of miscarriage. Participants who were female, highly educated, married and healthy gave significantly more correct responses. On the other hand, the majority wrongly assumed that a stressful event (65%) and long-standing stress (75%) to be causes of miscarriage. Participants who had no history of miscarriage as well as males answered significantly more incorrectly. Sixty-five percent of respondents thought that miscarriage occurred less than 15% of all pregnancies. Among respondents who had experienced miscarriage personally, 53 and 36% felt guilty and lonely, respectively. Many respondents blamed the woman for the miscarriage either in terms of her behavior or mental stress and considered the frequency of miscarriage to be lower than it actually is.

    更新日期:2019-11-26
  • Correction to: Investigation of novel variations of ORAI1 gene and their association with Kawasaki disease
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-07-31
    Kyaw Thiha, Yoichi Mashimo, Hiroyuki Suzuki, Hiromichi Hamada, Akira Hata, Toshiro Hara, Toshihiro Tanaka, Kaoru Ito, Yoshihiro Onouchi

    An amendment to this paper has been published and can be accessed via a link at the top of the paper

    更新日期:2019-11-18
  • Computational identification and analysis of early diagnostic biomarkers for kidney cancer
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-07-26
    Tang Tang, Xiaoyan Du, Xiaoyi Zhang, Wenling Niu, Chunhua Li, Jianjun Tan
    更新日期:2019-11-18
  • Comprehensive genetic analysis of 57 families with clinically suspected Cornelia de Lange syndrome
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-07-23
    Hiromi Aoi, Takeshi Mizuguchi, José Ricard Ceroni, Veronica Eun Hue Kim, Isabel Furquim, Rachel S. Honjo, Takuma Iwaki, Toshifumi Suzuki, Futoshi Sekiguchi, Yuri Uchiyama, Yoshiteru Azuma, Kohei Hamanaka, Eriko Koshimizu, Satoko Miyatake, Satomi Mitsuhashi, Atsushi Takata, Noriko Miyake, Satoru Takeda, Atsuo Itakura, Débora R. Bertola, Chong Ae Kim, Naomichi Matsumoto
    更新日期:2019-11-18
  • Complete genome and bimodal genomic structure of the amoebal symbiont Neochlamydia strain S13 revealed by ultra-long reads obtained from MinION
    J. Hum. Genet. (IF 3.545) Pub Date : 2019-11-14
    Junya Yamagishi, Kyoko Hayashida, Junji Matsuo, Torahiko Okubo, Makoto Kuroda, Hiroki Nagai, Tsuyoshi Sekizuka, Hiroyuki Yamaguchi, Chihiro Sugimoto
    更新日期:2019-11-14
  • Cloning and characterization of human and mouse PROSC (proline synthetase co-transcribed) genes.
    J. Hum. Genet. (IF 3.545) Pub Date : 1999-09-25
    S Ikegawa,M Isomura,Y Koshizuka,Y Nakamura

    Large-scale DNA sequencing, coupled with in silico gene trapping, is a robust approach to identifying unknown genes in selected genomic regions. Using this approach we have isolated a novel human gene, PROSC (for proline synthetase co-transcribed [bacterial homolog]), from human chromosome 8p11.2, and its mouse counterpart. The human PROSC gene spanned 17 kb of genomic DNA; its cDNA was 2530 bp long, with 8 exons that included an open reading frame of 825 bp (275 amino acids). The mouse cDNA (Prosc), 1995 bp long, was predicted to encode 274 amino acids. PROSC is ubiquitously expressed in human tissues and has been highly conserved among divergent species from bacteria to mammals, suggesting its important cellular function. The gene product is likely to be a soluble cytoplasmic protein, but its function remains to be determined.

    更新日期:2019-11-01
  • Dlx5, the mouse homologue of the human-imprinted DLX5 gene, is biallelically expressed in the mouse brain.
    J. Hum. Genet. (IF 3.545) Pub Date : 2004-09-15
    Motoshi I Kimura,Yasuhiro Kazuki,Akiko Kashiwagi,Yoshiteru Kai,Satoshi Abe,Ottavia Barbieri,Giovanni Levi,Mitsuo Oshimura

    The mouse Dlx5 gene encodes a distal-less-related DNA-binding homeobox protein first expressed during early embryonic development in anterior regions of mouse embryo and is located on chromosome 6, which is the syntenic region to the human chromosome 7q21-q31 imprinting cluster. Recently, its human homologue, DLX5, was identified to be imprinted and maternally expressed, at least in normal human lymphoblasts and in brain tissues. In our study, we analyzed the imprinting status of mouse Dlx5 by RT-PCR, first in the F1 of a reciprocal cross between two different mouse strains, and second in heterozygous Dlx5 mutant mice. Both approaches revealed that mouse Dlx5 followed a biallelic pattern of expression in brain tissue and in testis. Our findings suggest that the Dlx5 gene escapes genomic imprinting, at least in mice of certain genetic backgrounds.

    更新日期:2019-11-01
  • Haplotype architecture of the norepinephrine transporter gene SLC6A2 in four populations.
    J. Hum. Genet. (IF 3.545) Pub Date : 2004-09-15
    Inna Belfer,Gabriel Phillips,Julie Taubman,Heather Hipp,Robert H Lipsky,Mary-Anne Enoch,Mitchell B Max,David Goldman

    The norepinephrine transporter (NET) regulates levels of monoamine neurotransmitters integral to a variety of behaviors and autonomic functions. Two SLC6A2 polymorphisms have been used in genetic association studies, generating intriguing but nondefinitive results on traits such as hypertension and mood. One of these SLC6A2 variants is functional but rare. The other is common but not informative over the entire 48 kb SLC6A2 region and is insufficient to capture the functional diversity potentially contained within any SLC6A2 region. To elucidate SLC6A2 haplotype structure and define markers sufficient to capture haplotype diversity within detected haplotype blocks, 26 single-nucleotide polymorphisms (SNPs) were genotyped in 384 individuals evenly divided across Finnish Caucasian, US Caucasian, Plains American Indian, and African American populations. Three conserved blocks, 13.6, 12.5, and 25 kb in size and showing little evidence for historical recombination were observed in all populations. Haplotype diversity in block 1 and numbers of common haplotypes were highest in African Americans, among whom 5-6 optimal markers were sufficient to maximize diversity of each block. For other populations, 2-3 markers/block sufficed, but the optimal markers differed across populations. The SLC6A2 haplotype map and 25-marker panel (excluding the monomorphic one) is a comprehensive tool for genetic linkage studies on phenotypes related to NET function.

    更新日期:2019-11-01
  • Mutations in the gene encoding KIAA1199 protein, an inner-ear protein expressed in Deiters' cells and the fibrocytes, as the cause of nonsyndromic hearing loss.
    J. Hum. Genet. (IF 3.545) Pub Date : 2003-10-25
    Satoko Abe,Shin-ichi Usami,Yusuke Nakamura

    We report three possibly disease-causing point mutations in one of the inner-ear-specific genes, KIAA1199. We identified an R187C mutation in one family, an R187H mutation in two unrelated families, and an H783Y mutation in one sporadic case of nonsyndromic hearing loss. In situ hybridization indicated that the murine homolog of KIAA1199 mRNA is expressed specifically in Deiters' cells in the organ of Corti at postnatal day zero (P n) P0 before the onset of hearing, but expression in those cells disappears by day P7. The signal of KIAA1199 was also observed in fibrocytes of the spiral ligament and the spiral limbus through to P21, when the murine cochlea matures. Thus, the gene product may be involved in uptake of potassium ions or trophic factors with a particular role in auditory development. Although the R187C and R187H mutations did not appear to affect subcellular localization of the gene product in vitro, the H783Y mutation did present an unusual cytoplasmic distribution pattern that could underlie the molecular mechanism of hearing impairment. Our data bring attention to a novel candidate for hearing loss and indicate that screening of mutations in inner-ear-specific genes is likely to be an efficient approach to finding genetic elements responsible for deafness.

    更新日期:2019-11-01
  • Resequencing of the characterised CTGF gene to identify novel or known variants, and analysis of their association with diabetic nephropathy.
    J. Hum. Genet. (IF 3.545) Pub Date : 2006-02-28
    Amy Jayne McKnight,David A Savage,Chris C Patterson,Hugh R Brady,A Peter Maxwell

    Connective tissue growth factor (CTGF) has been implicated in the pathogenesis of diabetic nephropathy; however, to date there have been no reports of genomic analysis on this gene. The CTGF gene was comprehensively screened using WAVE (dHPLC) technology and direct capillary sequencing. Single nucleotide polymorphisms (SNPs) with minor allele frequencies greater than 5% were further investigated in an Irish, type 1 diabetic population. The case-control collection consisted of 272 diabetics with nephropathy and 367 non-nephropathic diabetic controls who were genotyped using TaqMan and Pyrosequencing technologies. Ten SNPs were identified, of which seven were novel. Four SNPs are located in the promoter, one in exon 2, two in intron 2 and three in the 3' untranslated region. Based on in silico analysis, three SNPs, c.-650G>C, c.-484T>C and c.247G>C, are potentially functional. Subsequent statistical analysis for common SNPs, c.-650G>C, c.-420InsT, c.-220G>C, c.289+94T>C and c.289+98T>C, in the case-control study revealed no significant differences in genotype or allele frequencies. CTGF has emerged as a biological candidate gene for diabetic nephropathy; however, no significant association was detected between common CTGF SNPs and nephropathy in this population.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Evaluation of the association between polymorphisms at the DRD2 locus and stuttering.
    J. Hum. Genet. (IF 3.545) Pub Date : 2011-03-11
    Changsoo Kang,Bianca Santos Domingues,Eduardo Sainz,Carlos Eduardo Frigério Domingues,Dennis Drayna,Danilo Moretti-Ferreira

    更新日期:2019-11-01
  • Chromosome 17q21 SNP and severe asthma.
    J. Hum. Genet. (IF 3.545) Pub Date : 2010-10-29
    Aristea Binia,Nadia Khorasani,Pankaj K Bhavsar,Ian Adcock,Chris E Brightling,K Fan Chung,William O C Cookson,Miriam F Moffatt

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • 更新日期:2019-11-01
  • A novel DFNA5 mutation does not cause hearing loss in an Iranian family.
    J. Hum. Genet. (IF 3.545) Pub Date : 2007-04-12
    Lut Van Laer,Nicole C Meyer,Mahdi Malekpour,Yasser Riazalhosseini,Mahdi Moghannibashi,Kimia Kahrizi,Ann Vandevelde,Fatemeh Alasti,Hossein Najmabadi,Guy Van Camp,Richard J H Smith

    Mutations in DFNA5 lead to autosomal dominant non-syndromic sensorineural hearing loss that starts at the high frequencies. To date, only three DFNA5 mutations have been described, and although different at the genomic DNA level, all lead to exon 8 skipping at the mRNA level. This remarkable fact has led towards the hypothesis that DFNA5-associated hearing loss is caused by a gain-of-function mutation and not by haplo-insufficiency as previously thought. Here, we describe a fourth DFNA5 mutation: the insertion of a cytosine at nucleotide position 640 (AF073308.1:_c.640insC, AAC69324.1:_p. Thr215HisfsX8). Unlike the previously described mutations, this frameshift mutation truncates the protein in exon 5 of the gene. Although the mutation was found in an extended Iranian family with hereditary hearing loss, it does not segregate with the hearing loss phenotype and is even present in persons with normal hearing. This fact provides further support for the hypothesis that DFNA5-associated hearing loss is caused by a gain-of-function mutation.

    更新日期:2019-11-01
  • The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage.
    J. Hum. Genet. (IF 3.545) Pub Date : 2006-08-10
    Yoshiko Masuda,Manabu Futamura,Hiroki Kamino,Yasuyuki Nakamura,Noriaki Kitamura,Shiho Ohnishi,Yuji Miyamoto,Hitoshi Ichikawa,Tsutomu Ohta,Misao Ohki,Tohru Kiyono,Hiroshi Egami,Hideo Baba,Hirofumi Arakawa

    The tumor suppressor p53 plays a crucial role in the cellular response to DNA damage by transcriptional activation of numerous downstream genes. Although a considerable number of p53 target genes have been reported, the precise mechanism of p53-regulated tumor suppression still remains to be elucidated. Here, we report a novel role of the DFNA5 gene in p53-mediated etoposide-induced cell death. The DFNA5 gene has been previously reported to be responsible for autosomal-dominant, nonsyndromic hearing impairment. The expression of the DFNA5 gene was strongly induced by exogenous and endogenous p53. The chromatin immunoprecipitation assay indicated that a potential p53-binding sequence is located in intron 1 of the DFNA5 gene. Furthermore, the reporter gene assay revealed that the sequence displays p53-dependent transcriptional activity. The ectopic expression of DFNA5 enhanced etoposide-induced cell death in the presence of p53; however, it was inhibited in the absence of p53. Finally, the expression of DFNA5 mRNA was remarkably induced by gamma-ray irradiation in the colon of p53(+/+) mice but not in that of p53(-/-) mice. These results suggest that DFNA5 plays a role in the p53-regulated cellular response to genotoxic stress probably by cooperating with p53.

    更新日期:2019-11-01
  • Characterization of the human nasal embryonic LHRH factor gene, NELF, and a mutation screening among 65 patients with idiopathic hypogonadotropic hypogonadism (IHH).
    J. Hum. Genet. (IF 3.545) Pub Date : 2004-09-15
    Kiyonori Miura,James S Acierno,Stephanie B Seminara

    As the mouse nasal embryonic LHRH factor gene (Nelf) encodes a guidance molecule for the migration of the olfactory axon and gonadotropin-releasing hormone neurons, its human homolog, NELF, is a candidate gene for Kallmann syndrome, a disease of idiopathic hypogonadotropic hypogonadism (IHH) with anosmia or hyposmia. We report here characterization of NELF and results of mutation analysis in 65 IHH patients. Assembling EST clones, RACE, and sequencing showed that NELF mapped to 9q34.3 is composed of 16 exons and 15 introns with a 1,590-bp ORF encoding 530 amino acids. RT-PCR on a fetal brain cDNA library revealed five alternatively spliced variants. Among them, NELF-v1 has 93-94% identity at the amino acid level to mouse/rat Nelf, and four other transcripts are also highly conserved among the three species. A 3.0-kb transcript is expressed most highly in the adult and fetal brain, testis, and kidney, indicating that NELF plays a role in the function of these tissues. Mutation screening detected in a patient with IHH one novel heterozygous missense mutation (1438A>G, T480A) at the donor-splice site in exon 15 of NELF. As this mutation was not found in 100 normal control individuals, T480A may be associated with IHH. Four other novel SNPs (102C > T and 1029C > T within the coding region, and two IVS14+47C > T and IVS15+41G > A) were also identified in NELF.

    更新日期:2019-11-01
  • The role of the IKAP gene polymorphisms in atopic diseases in the middle European population.
    J. Hum. Genet. (IF 3.545) Pub Date : 2003-05-30
    Marcel Schüller,Lydie Izakovicová Hollá,Dana Bucková,Vladimír Znojil,Marcel Stelcl,Ondrej Rybnícek,Jirí Vácha

    Over ten genome-wide screens and many candidate genes studies were performed worldwide to elucidate genetic factors involved in the pathogenesis of bronchial asthma and other atopic diseases. Results from these studies were often discordant, which might have reflected complexity and heterogeneity of these multifactorial diseases. Among a variety of other loci, specific variants of the gene for IKAP (IKK complex-associated protein) were shown to be associated with bronchial asthma in children in a Japanese study. To test the possible role of SNPs in the coding region of the IKAP gene in atopic asthma or other atopic phenotypes in a highly homogenous Czech population, a case-control study including 373 patients and 309 healthy control subjects was performed. There were no significant differences in the genotype and allele distributions for any of five SNPs in the IKAP gene (T819C, G2295A, A2490G, T3214A and C3473T) between patients with atopic asthma or other atopic diseases and healthy controls. These results suggest that the polymorphisms in the coding region of the IKAP gene are unlikely to contribute to atopic disease risk in the Czech population.

    更新日期:2019-11-01
  • Amino-acid substitutions in the IKAP gene product significantly increase risk for bronchial asthma in children.
    J. Hum. Genet. (IF 3.545) Pub Date : 2001-04-03
    S Takeoka,M Unoki,Y Onouchi,S Doi,H Fujiwara,A Miyatake,K Fujita,I Inoue,Y Nakamura,M Tamari

    The complex etiology of bronchial asthma (BA), one of the most common inflammatory diseases throughout the world, involves a combination of various genetic and environmental factors. A number of investigators have undertaken linkage and association studies to shed light on the genetic background of BA, but the genetic aspects of this disease are still poorly understood. In the course of a project to screen the entire human genome for single nucleotide polymorphisms (SNPs) that might represent useful markers for large-scale association analyses of common diseases and pharmacogenetic traits, we identified six SNPs within the gene encoding I-kappaB-associated protein (IKAP), a regulator of the NF-kappaB signal pathway. Most of these SNPs were in linkage disequilibrium with each other. We observed a strong allelic association between BA in childhood and two of the SNP sites, T3214A (Cys1072Ser) and C3473T (Pro1158Leu); P = 0.000004 for T3214A and P = 0.0009 for C3473T. T3214A was also associated with BA in adult patients (P = 0.000002), but C3473T was not (P = 0.056). To confirm the above results, we compared estimated frequencies of haplotypes of the six SNPs between BA patients and controls. We found a strong association between BA in childhood and a specific haplotype, TGAAAT, that involved two amino-acid substitutions (819T, 2295G, 2446A, 2490A, 3214A, and 3473T; P = 0.00004, odds ratio, 2.94; 95% confidence interval [CI], 2.48-3.4). On the other hand, haplotype TACGTC, which differed from the TGAAAT haplotype in the last five nucleotides, was inversely correlated with the BA phenotype (P = 0.002; odds ratio, 9.83; 95% CI, 8.35-11.31). These results indicated that specific variants of the IKAP gene, or a variant in linkage disequilibrium with the TGAAAT haplotype, might be associated with mechanisms responsible for early-onset BA.

    更新日期:2019-11-01
  • Mutational analysis of the RET proto-oncogene in 71 Japanese patients with medullary thyroid carcinoma.
    J. Hum. Genet. (IF 3.545) Pub Date : 1998-06-11
    S Shirahama,K Ogura,H Takami,K Ito,T Tohsen,A Miyauchi,Y Nakamura

    Multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial medullary thyroid carcinomas (FMTC) are caused by germline mutations in the RET proto-oncogene. To investigate the spectrum of RET mutations among Japanese patients, we screened the RET gene in 71 patients with thyroid carcinomas. The panel included representatives of 44 families carrying FMTC or MEN2, 22 sporadic medullary thyroid carcinomas (MTCs), and five MTCs without familial information. Mutations in nucleotide sequences encoding one of three specific cysteine residues in the extracellular domain of the RET protein were found in 33 of the 34 MEN2A patients and in five of the six FMTC patients examined. A mutation at codon 918, causing the substitution of threonine for methionine in the tyrosine kinase domain of the protein, was found in germline DNAs of all four patients with MEN2B and in two of the 22 patients with sporadic MTCs; codon 918 was mutated somatically in tumor DNAs from three other sporadic cases. Germline mutations of codon 768, GAG to GAC (Glu to Asp), were detected in one FMTC, in one patient with sporadic MTC, and in one of the patients without familial information. Two somatic mutations, an Asp to Gly substitution at codon 631 and a Cys to Arg substitution at codon 634, had not been reported previously. Of five germline mutations found among the 22 sporadic cases, four were confirmed as de novo mutations since in each case neither parent carried the mutation. As nearly one-fourth of the patients with sporadic MTCs carried germline mutations and 50% of their children are expected to develop MTC and other endocrine tumors, these results indicated the importance of careful clinical surveillance of family members of any patient with MTC.

    更新日期:2019-11-01
  • Impaired interactions between mouse Eyal harboring mutations found in patients with branchio-oto-renal syndrome and Six, Dach, and G proteins.
    J. Hum. Genet. (IF 3.545) Pub Date : 2002-04-13
    Hidenori Ozaki,Yoko Watanabe,Keiko Ikeda,Kiyoshi Kawakami

    Mutations in the EYA1 gene are responsible for branchio-oto-renal (BOR) syndrome as well as for other ocular defects. Most of the mutations are located within or in the vicinity of the EYA domain, which is highly conserved in the EYA protein family. The EYA domain is required for protein-protein interactions, which are important to the biological function of EYA proteins. To determine how EYA1 mutations cause BOR syndrome and/or ocular defects, we tested the effects of Eya1 mutations on interactions with Six. Dach, and G proteins by mammalian two-hybrid and GST-pulldown assays. Defective interactions were noted between BOR-type mutations S486P and L504R of Eya1 and Dach1, G proteins, and some Six proteins. These mutations impaired the activation of transcription from a Six-responsive gene, myogenin, with Six5. S486P and L504R showed an altered digestion pattern with trypsin, and L504R also decreased the sensitivity to V8 protease digestion and produced a peptide fragment with a different M(r). Our results suggest that defective protein-protein interactions of the mutations in the EYA domain underlie BOR syndrome and that SIX, DACH, and/or G proteins are possibly involved in the pathogenic processes.

    更新日期:2019-11-01
  • Corrigendum: Novel KCNB1 mutation associated with non-syndromic intellectual disability.
    J. Hum. Genet. (IF 3.545) Pub Date : 2017-04-26
    Xénia Latypova,Naomichi Matsumoto,Cécile Vinceslas-Muller,Stéphane Bézieau,Bertrand Isidor,Noriko Miyake

    更新日期:2019-11-01
  • Erratum: PARS2 and NARS2 mutations in infantile-onset neurodegenerative disorder.
    J. Hum. Genet. (IF 3.545) Pub Date : 2017-02-17
    Takeshi Mizuguchi,Mitsuko Nakashima,Mitsuhiro Kato,Keitaro Yamada,Tohru Okanishi,Nina Ekhilevitch,Hanna Mandel,Ayelet Eran,Miyuki Toyono,Yukio Sawaishi,Hirotaka Motoi,Masaaki Shiina,Kazuhiro Ogata,Satoko Miyatake,Noriko Miyake,Hirotomo Saitsu,Naomichi Matsumoto

    更新日期:2019-11-01
  • Identification of brain-specific splicing variants of the hDLG1 gene and altered splicing in neuroblastoma cell lines.
    J. Hum. Genet. (IF 3.545) Pub Date : 1998-06-11
    K Mori,K Iwao,Y Miyoshi,A Nakagawara,K Kofu,T Akiyama,N Arita,T Hayakawa,Y Nakamura

    The human homologue of Drosophila tumor suppressor dlg, hDLG1, is one of the proteins known to interact with APC, a tumor suppressor for colorectal cancer. Alternative splicing of this gene generates transcripts either with [insertion 1 (I1)] or without 99 nucleotides in the 5' part of the dlg homology repeats (DHR) domain. We found almost equivalent expression of these two splicing variants in most human tissues; however, in skeletal muscle the transcript with the 99-bp insertion was predominant, and in the brain, that without the 99-bp insertion was expressed predominantly. We also examined alternative splicing in the region between the SH3 and GUK domains where two different sizes of insertions, 34 nucleotides (I2) or 100 nucleotides (I3), had been reported, and found various splicing patterns among the tissues examined. In brain we detected six different, alternatively spliced transcripts, two of which included a novel, 36-bp, brain-specific exon encoding a peptide bearing significant homology to a portion of rat synapse-associated protein, SAP97/PSD95. Subsequently, we investigated the splicing patterns of the hDLG1 gene in 24 neuroblastoma cell lines. In two-thirds of these lines, the splicing patterns were altered from those observed in normal brain tissue. As one-third retained the normal brain-splicing pattern, the loss of normal splicing of hDLG1 may not in itself cause formation of tumors, but it might reflect the biological character of individual neuroblastomas.

    更新日期:2019-11-01
  • Isolation and characterization of a human cDNA homologous to the Xenopus laevis XCAP-C gene belonging to the structural maintenance of chromosomes (SMC) family.
    J. Hum. Genet. (IF 3.545) Pub Date : 1999-05-13
    T Nishiwaki,Y Daigo,T Kawasoe,Y Nagasawa,H Ishiguro,M Fujita,Y Furukawa,Y Nakamura

    We have isolated a human cDNA encoding a protein of 1288 amino acids that shows 77% identity in amino acid sequence to XCAP-C, Xenopus chromosome-associated polypeptide-C, belonging to the family of structural maintenance of chromosomes (SMC), which is known to play a crucial role in the proper condensation and segregation of mitotic chromosomes. In particular, an almost 200-amino-acid domain in the N-terminal, including an NTP-binding motif and that in the C-terminal domain, including a DA-box, were well conserved and showed 95% identity between human and frog, indicating that these two domains are functionally very important. The transcript of this gene was expressed ubiquitously in various human tissues, but thymus, testis, and colon seemed to express this gene more abundantly. We also determined its chromosomal location at 3q26.1 by fluorescence in situ hybridization.

    更新日期:2019-11-01
  • Four mutations of the spastin gene in Japanese families with spastic paraplegia.
    J. Hum. Genet. (IF 3.545) Pub Date : 2006-06-22
    Rehana Basri,Ichiro Yabe,Hiroyuki Soma,Asako Takei,Hiroyuki Nishimura,Yuka Machino,Yasumasa Kokubo,Masafumi Kosugi,Ryuichirou Okada,Motohiro Yukitake,Hisao Tachibana,Yasuo Kuroda,Shigeki Kuzuhara,Hidenao Sasaki

    Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower limbs. HSP is caused by failure of development or selective degeneration of the corticospinal tracts, which contain the longest axons in humans. The most common form of HSP is caused by mutations of the spastin gene (SPAST), located on chromosome 2p21-p22, which encodes spastin, one of the ATPases associated with diverse cellular activities (AAA). In this study, we detected four causative mutations of SPAST among 14 unrelated patients with spastic paraplegia. Two missense mutations (1447A-->G, 1207C-->G) and two deletion mutations (1465delT, 1475-1476delAA) were located in the AAA cassette region. Three of these four mutations were novel. Previous reports and our results suggest that the frequency of SPAST mutations is higher among Japanese patients with autosomal dominant HSP, although SPAST mutations are also observed in patients with sporadic spastic paraplegia.

    更新日期:2019-11-01
  • A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia.
    J. Hum. Genet. (IF 3.545) Pub Date : 2002-08-31
    Chang-Seok Ki,Won Yong Lee,Do Hoon Han,Duk Hyun Sung,Kyung-Bok Lee,Kyung-A Lee,Sang Seon Cho,Seunghee Cho,Hyokkee Hwang,Kwang Min Sohn,Yeun Joo Choi,Jong-Won Kim

    Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower extremities. Among eight loci linked with autosomal-dominant (AD)-HSP, the SPG4 locus on chromosome 2p22 accounts for about 40% of all patients. Recently, mutations in a new member of the AAA protein family, called spastin, have been identified as responsible for SPG4-linked AD-HSP. Here, we describe a novel missense mutation (c.1031T>A; I344K) in exon 7 of the SPG4 gene identified in a Korean family with typical clinical features of pure AD-HSP. The mutation affects the third amino acid of the highly conserved AAA cassette domain, which is the most fore part of the domain altered by a missense mutation reported so far. Clinical presentations of affected individuals carrying the I344K mutation were not different from those of pure AD-HSP with SPG4 mutations reported previously. However, it is noteworthy that neither urinary dysfunction nor involvement of upper extremities was noticed in this family. To our knowledge, this is the first report of genetically confirmed AD-HSP in Korea.

    更新日期:2019-11-01
  • Two families with Wilson disease in which siblings showed different phenotypes.
    J. Hum. Genet. (IF 3.545) Pub Date : 2002-10-12
    Yukiko Takeshita,Norikazu Shimizu,Yukitoshi Yamaguchi,Hiroki Nakazono,Miyuki Saitou,Yoshinao Fujikawa,Tsugutoshi Aoki

    We investigated two families with Wilson disease in which siblings showed different clinical phenotypes and different ages at onset. In Family 1, the second and fourth male children demonstrated onset of the neurological type of Wilson disease at 16 and 28 years of age, respectively, and the first female child developed the hepatic type at 38 years of age. In Family 2, the second male child showed neurological symptoms at 32 years of age and was diagnosed as having the hepatoneurological type of Wilson disease; then the 35-year-old first female child was found to have the hepatic type by familial screening. We performed mutation analysis of the ATP7B gene for these patients, and found that the mutation was a compound heterozygote in both families. Previous reports of siblings with Wilson disease have shown an identical clinical phenotype and similar ages at onset. In addition, hepatic-type cases generally occur at lower ages compared with the neurological type. In the present investigation, however, younger patients showed neurological symptoms earlier than their older siblings, and clinical phenotypes differed among siblings in both families. These cases appear to be rare. Individual differences in copper accumulation in hepatic cells and intolerance to copper toxicity might be the reason for this phenomenon. Furthermore, there might be a difference in the dominance of the allele expressing ATP7B protein among these cases, resulting in different clinical phenotypes, because all patients of both families were found to be compound heterozygotes.

    更新日期:2019-11-01
  • Novel mutation of L718X in the ATP7A gene in a Japanese patient with classical Menkes disease, and four novel polymorphisms in the Japanese population.
    J. Hum. Genet. (IF 3.545) Pub Date : 2000-10-24
    A Ogawa,S Yamamoto,M Kanazawa,E Ogawa,M Takayanagi,S Hasegawa,Y Kohno

    Menkes disease is an X-linked recessive disorder of the copper membrane transport system caused by mutations in the ATP7A gene. While various mutations in the ATP7A gene have been reported, a genotype-phenotype correlation has not been clearly defined. A novel mutation in the ATP7A gene in a Japanese patient with classical Menkes disease was identified via analysis of reverse-transcriptase polymerase chain reaction products and genomic DNA of the ATP7A gene. The nonsense mutation, L718X, was found to result in premature termination and immature ATP7A protein, unlikely to have normal functioning. Therefore, this nonsense mutation of the ATP7A gene is proposed to play a causative role in presenting the classical Menkes phenotype. Furthermore, four novel polymorphisms, C1535T (L464L), C2151T (T669I), G2253A (R703H), and C3677T (H1178Y) were also identified.

    更新日期:2019-11-01
  • Molecular analysis of Wilson disease in Taiwan: identification of one novel mutation and evidence of haplotype-mutation association.
    J. Hum. Genet. (IF 3.545) Pub Date : 2000-10-24
    C C Lee,J Y Wu,F J Tsai,H Kodama,T Abe,C F Yang,C H Tsai

    Wilson disease (WND) is caused by a deficiency of the copper-transporting enzyme, P-type ATPase (ATP7B). Twelve different mutations have previously been identified in Taiwan Chinese with Wilson disease. We, herein, report another 4 missense mutations, 1 of which is novel. We did haplotype analysis of Taiwanese WND chromosomes, using three well characterized short tandem repeat markers (haplotype was assigned in the order of D13S314-D13S301-D13S316). Association correlation was found between the mutations and their respective haplotypes. Haplotype-deduced pedigree analysis was shown to be helpful in the mutation analysis of WND chromosomes and in the molecular assessment of both pre-symptomatic WND patients and carriers. Given the complexity and heterogeneity of the mutation spectrum of ATP7B, we suggest that haplotype analysis should be performed before full-scale mutation analysis.

    更新日期:2019-11-01
  • Novel mutations of the ATP7B gene in Japanese patients with Wilson disease.
    J. Hum. Genet. (IF 3.545) Pub Date : 2000-03-18
    Y Kusuda,K Hamaguchi,T Mori,R Shin,M Seike,T Sakata

    Wilson disease (WD) is an autosomal recessive disorder characterized by copper accumulation in the liver, brain, kidneys, and corneas, and culminating in copper toxication in these organs. In this study, we analyzed mutations of the responsible gene, ATP7B, in four Japanese patients with WD. By direct sequencing, we identified five mutations, of which two were novel, and 16 polymorphisms, of which 6 were novel. The mutations 2871delC and 2513delA shift the reading frame so that truncated abnormal protein is expected. In contrast to these mutations found in patients with hepatic-type of early onset, the mutations A874V, R778L, and 3892delGTC were either missense mutations or in frame 1-amino acid deletion, and occurred in the patients with hepato-neurologic type of late onset. The mutations 2871delC and R778L have been previously reported in a relatively large number of Japanese patients. In particular, R778L is known to be more prevalent in Asian countries than in other countries of the world. Our data are compatible with the hypothesis that the mutations tend to occur in a population-specific manner. Therefore, the accumulation of the types of mutations in Japanese patients with WD will facilitate the fast and effective genetic diagnosis of WD in Japanese patients.

    更新日期:2019-11-01
  • An Ile/Val polymorphism at codon 1464 of the ATP7A gene.
    J. Hum. Genet. (IF 3.545) Pub Date : 1999-11-26
    A Ogawa,S Yamamoto,M Takayanagi,T Kogo,M Kanazawa,Y Kohno

    An isoleucine/valine polymorphism was observed at codon 1464 of the ATP7A gene, which is thought to encode a copper transporting adenosine triphosphatase (ATPase). The frequency of Val1464 was estimated to be 5.7% in the Japanese population. This polymorphism may be useful in genetic studies of Menkes disease.

    更新日期:2019-11-01
Contents have been reproduced by permission of the publishers.
导出
全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
加州大学洛杉矶分校
上海纽约大学William Glover
南开大学化学院周其林
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug