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Causal effect of severe and non-severe malaria on dyslipidemia in African Ancestry individuals: A Mendelian randomization study Ann. Hum. Genet. (IF 1.9) Pub Date : 2024-03-15 Mariam Traore, Harouna Sangare, Oudou Diabate, Abdoulaye Diawara, Cheickna Cissé, Oyekanmi Nashiru, Jian Li, Jeffrey Shaffer, Mamadou Wélé, Seydou Doumbia, Tinashe Chikowore, Opeyemi Soremekun, Segun Fatumo
Dyslipidemia is becoming prevalent in Africa, where malaria is endemic. Observational studies have documented the long-term protective effect of malaria on dyslipidemia; however, these study designs are prone to confounding. Therefore, we used Mendelian randomization (MR, a method robust to confounders and reverse causation) to determine the causal effect of severe malaria (SM) and the recurrence of
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Genetically predicted retinal vascular occlusion in relation to cardiovascular diseases: A bidirectional two‐sample Mendelian randomization analysis Ann. Hum. Genet. (IF 1.9) Pub Date : 2024-02-19 Jun Zhang, Yiji Pan, Hongxia Yang, Shuqiong Hu, Sheng Zheng, Tao He
IntroductionIncreasing evidence implicates retinal vascular occlusions as a susceptibility factor for cardiovascular diseases (CVDs), whereas inconsistent results on the relationship were reported in previous observational studies. This research using a bidirectional two‐sample Mendelian randomization (MR) analysis aimed to investigate the potential association between genetically determined central/branch
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The systematic identification of survival‐related alternative splicing events and splicing factors in glioblastoma Ann. Hum. Genet. (IF 1.9) Pub Date : 2024-02-19 Tao Peng, Zhe Liu, Yu Zhang, Xudong Liu, Lijun Zhao, Ying Ma, Jinke Fan, Xinqiang Song, Lei Wang
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, making it one of the most life‐threatening human cancers. Nevertheless, research on the mechanism of action between alternative splicing (AS) and splicing factor (SF) or biomarkers in GBM is limited. AS is a crucial post‐transcriptional regulatory mechanism. More than 95% of human genes undergo AS events. AS can diversify
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Association of blood lipid profiles and asthma: A bidirectional two-sample Mendelian randomization study Ann. Hum. Genet. (IF 1.9) Pub Date : 2024-02-02 Yi-Shian Liu, Yu-Chun Lin, Meng-Chih Lin, Chao-Chien Wu, Tsu-Nai Wang
Observational studies and meta-analyses have indicated associations between blood lipid profiles and asthma. However, the causal association is unknown. Therefore, this study investigated the causal relationship between blood lipid profiles and asthma using bidirectional Mendelian randomization analysis.
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Investigation of the association between the Toll-like receptor 1 rs4833095 variation and gastric adenocarcinoma recurrence Ann. Hum. Genet. (IF 1.9) Pub Date : 2024-01-09 Yuan Dang, Jingyun Huang, Chen Lin, Shaohua Xu
Toll-like receptors (TLRs) are a family of transmembrane receptors that play key roles in identifying invading pathogens and activating innate immunity. TLR1 has been reported to be associated with the risk of gastric cancer (GC) but that was based on only a simple statistical analysis.
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ABCA1 variant rs9282541 is associated with metabolic syndrome in Maya children Ann. Hum. Genet. (IF 1.9) Pub Date : 2024-01-09 Barbara I. Peña-Espinoza, Emmanuel Torre-Horta, María G. Ortiz-López, Marta Menjivar
Metabolic syndrome (MetS) is a metabolic disorder encompassing risk factors for cardiovascular disease and type 2 diabetes (T2D). In Mexico, the MetS is a national health problem in adults and children. Environmental and genetic factors condition the MetS. However, studies to elucidate the contribution of genetic factors to MetS in Mexico are scarce. A recent study showed that variant rs9282541 (A-allele)
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Nonsense suppression induces read-through of a novel BMPR1A variant in a Chinese family with hereditary colorectal cancer Ann. Hum. Genet. (IF 1.9) Pub Date : 2024-01-09 Zhaokun Wang, Jiaying Shi, Dachang Tao, Shengyu Xie, Yuan Yang, Yunqiang Liu
BMPR1A-mediated signaling transduction plays an essential role in intestinal growth. Variations of BMPR1A lead to a rare autosomal dominant inherited juvenile polyposis syndrome (JPS) with high probability of developing into colorectal cancer (CRC). Nonsense and frameshift variations, generating premature termination codons (PTCs), are the most pathogenic variants in the BMPR1A gene.
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A comprehensive review of HVS-I mitochondrial DNA variation of 19 Iranian populations Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-12-31 Motahareh Amjadi, Zahra Hayatmehr, Balázs Egyed, Mahmood Tavallaei, Anna Szécsényi-Nagy
Iran is located along the Central Asian corridor, a natural artery that has served as a cross-continental route since the first anatomically modern human populations migrated out of Africa. We compiled and reanalyzed the HVS-I (hypervariable segment-I) of 3840 mitochondrial DNA (mtDNA) sequences from 19 Iranian populations and from 26 groups from adjacent countries to give a comprehensive review of
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Exploring the clinical significance of miR-148 expression variations in distinct subtypes of irritable bowel syndrome Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-12-31 Qun Ji, Fengxia Du, Yangyaxin Yu, Ying Li
Irritable bowel syndrome (IBS) belongs to chronic functional gastrointestinal diseases featured by abdominal pain and changes in bowel habits. This study aimed to investigate the clinical significance of serum miR-148 expression in different subtypes of IBS. We enrolled 86 IBS patients and 55 healthy controls. miR-148 expression levels were assessed in IBS patients classified into IBS-constipation
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Using the Bayesian variational spike and slab model in a genome-wide association study for finding associated loci with bipolar disorder Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-12-31 Maryam Kazemi Naeini, Mahdi Akbarzadeh, Iraj Kazemi, Doug Speed, Sayed Mohsen Hosseini
The genome-wide association studies (GWAS) analysis, the most successful technique for discovering disease-related genetic variation, has some statistical concerns, including multiple testing, the correlation among variants (single-nucleotide polymorphisms) based on linkage disequilibrium and omitting the important variants when fitting the model with just one variant. To eliminate these problems in
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Molecular and computational characterization of ABCB11 and ABCG5 variants in Tunisian patients with neonatal/infantile low-GGT intrahepatic cholestasis: Genetic diagnosis and genotype–phenotype correlation assessment Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-12-18 Boudour Khabou, Fakhri Kallabi, Rim Ben Abdelaziz, Ines Maaloul, Hajer Aloulou, Amel ben Chehida, Thouraya Kammoun, Veronique Barbu, Tahya Sellami Boudawara, Faiza Fakhfakh, Bassem Khemakhem, Olfa Siala Sahnoun
Many inherited conditions cause hepatocellular cholestasis in infancy, including progressive familial intrahepatic cholestasis (PFIC), a heterogeneous group of diseases with highly overlapping symptoms. In our study, six unrelated Tunisian infants with PFIC suspicion were the subject of a panel–target sequencing followed by an exhaustive bioinformatic and modeling investigations. Results revealed five
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Expression analysis of NF1-mutated alleles in a rare compound heterozygous spinal NF1 patient by digital PCR Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-11-28 Paola Bettinaglio, Viviana Tritto, Rosina Paterra, Marica Eoli, Paola Riva
Neurofibromatosis type 1 (NF1) is a heterogeneous neurocutaneous disorder. Spinal neurofibromatosis (SNF) is a distinct clinical entity of NF1, characterized by bilateral neurofibromas involving all spinal nerve roots. Although both forms are caused by intragenic heterozygous variants of NF1, missense variants have been associated with SNF, according to a dominant inheritance model causing haploinsufficiency
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The prevalence and linkage disequilibrium of 21 genetic variations related to thrombophilia, folate cycle, and hypertension in reproductive age women of Rostov region (Russia) Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-11-09 Oksana Yurievna Bordaeva, Ekaterina Grigorievna Derevyanchuk, Dema Alset, Maria Aleksandrovna Amelina, Tatiana Pavlovna Shkurat
Several maternal genetic variations are known to play an important role during pregnancy since they can affect mother health and/or fetal growth. The frequency of these variants is variable among different populations. This study aimed to investigate thrombophilia, folate metabolism and hypertension genetic variants in reproductive age women of Rostov region (Russia) and then assess their linkage disequilibrium
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The effect of TRIM5 variants on the susceptibility to HIV-1 infection and disease progression in the Polish population Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-11-09 Jolanta Bratosiewicz-Wąsik, Maria Miklasińska-Majdanik, Tomasz J. Wąsik
Tripartite motif containing 5α protein is a factor contributing to intracellular defense mechanisms against human immunodeficiency virus-1 (HIV-1) infection. The studies of TRIM5 variants effects on the risk of HIV-1 infection and the clinical course of disease provided inconclusive results in different ethnic groups. The aim of this study was to investigate the influence of TRIM5 variants on susceptibility
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A comprehensive meta-analysis to identify susceptibility genetic variants for precocious puberty Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-11-06 Xiuli Gu, Weining Xiong, Yan Yang, Honggang Li, Chengliang Xiong
Currently, several genetic variants in ERα gene (rs2234693 and rs9340799), ERβ gene (rs1256049 and rs4986938), KISS1 gene (rs4889, rs1132506 and rs5780218), LIN28B gene (rs314263, rs314276 and rs314280), and MKRN3 gene (rs2239669) have been repeatedly explored for their contribution to precocious puberty (PP) susceptibility. However, the results remain conflicting rather than conclusive. We here performed
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Phenotypic variability in Joubert syndrome is partially explained by ciliary pathophysiology Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-11-03 Joshua w. Owens, Robert J. Hopkin, Lisa J. Martin, Andrew Kodani, Brittany N. Simpson
Introduction: Joubert syndrome (JS) arises from defects of primary cilia resulting in potential malformations of the brain, kidneys, eyes, liver, and limbs. Several of the 35+ genes associated with JS have recognized genotype/phenotype correlations, but most genes have not had enough reported individuals to draw meaningful conclusions.
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The molecular structure and function of fibrocystin, the key gene product implicated in autosomal recessive polycystic kidney disease (ARPKD) Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-10-31 Travis A K Bannell, Joseph J B Cockburn
Autosomal recessive polycystic kidney disease is an early onset inherited hepatorenal disorder affecting around 1 in 20,000 births with no approved specific therapies. The disease is almost always caused by variations in the polycystic kidney and hepatic disease 1 gene, which encodes fibrocystin (FC), a very large, single-pass transmembrane glycoprotein found in primary cilia, urine and urinary exosomes
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Functions of cilia in cardiac development and disease Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-10-23 Wasay Mohiuddin Shaikh Qureshi, Kathryn E. Hentges
Errors in embryonic cardiac development are a leading cause of congenital heart defects (CHDs), including morphological abnormalities of the heart that are often detected after birth. In the past few decades, an emerging role for cilia in the pathogenesis of CHD has been identified, but this topic still largely remains an unexplored area. Mouse forward genetic screens and whole exome sequencing analysis
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An indel introduced by Neanderthal introgression, rs3835124:ATTTATT > ATT, might contribute to prostate cancer risk by regulating PDK1 expression Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-10-17 Ying Chen, Xin-Yi Yu, Shuang-Jia Xu, Xiao-Qian Shi, Xin-Xin Zhang, Chang Sun
Prostate cancer is one of the most common cancer types in males and rs12621278:A > G has been suggested to be associated with this disease by previous genome-wide association studies. One thousand genomes project data analysis indicated that rs12621278:A > G is within two long-core haplotypes. However, the origin, causal variant(s), and molecular function of these haplotypes were remaining unclear
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Low-pass whole genome sequencing is a reliable and cost-effective approach for copy number variant analysis in the clinical setting Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-10-09 Patricia C. Mazzonetto, Darine Villela, Silvia Souza da Costa, Ana C. V. Krepischi, Fernanda Milanezi, Michele P. Migliavacca, Paulo M. Pierry, Adriano Bonaldi, Luiz Gustavo D. Almeida, Camila Alves De Souza, José Eduardo Kroll, Marcelo G. Paula, Rodrigo Guarischi-Sousa, Cristovam Scapulatempo-Neto, Carla Rosenberg
Next generation sequencing technology has greatly reduced the cost and time required for sequencing a genome. An approach that is rapidly being adopted as an alternative method for CNV analysis is the low-pass whole genome sequencing (LP-WGS). Here, we evaluated the performance of LP-WGS to detect copy number variants (CNVs) in clinical cytogenetics.
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Clinical application of prospective whole-exome sequencing in the diagnosis of genetic disease: Experience of a regional disease center in South Korea Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-10-05 Ja Young Lee, Seung-Hwan Oh, Changwon Keum, Bo Lyun Lee, Woo Yeong Chung
Next-generation sequencing helps clinicians diagnose patients with suspected genetic disorders. The current study aimed to investigate the diagnostic yield and clinical utility of prospective whole-exome sequencing (WES) in rare diseases.
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Racgap1 knockdown results in cells with multiple cilia due to cytokinesis failure Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-09-28 Basudha Basu, Alice V. R. Lake, Becky China, Katarzyna Szymanska, Gabrielle Wheway, Sandra Bell, Ewan Morrison, Jacquelyn Bond, Colin A. Johnson
Most mammalian cells have a single primary cilium that acts as a signalling hub in mediating cellular functions. However, little is known about the mechanisms that result in aberrant supernumerary primary cilia per cell. In this study, we re-analysed a previously published whole-genome siRNA-based reverse genetic screen for genes mediating ciliogenesis to identify knockdowns that permit multi-ciliation
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Population stratification correction using Bayesian shrinkage priors for genetic association studies Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-09-28 Zilu Liu, Asuman S. Turkmen, Shili Lin
Population stratification (PS) is a major source of confounding in population-based genetic association studies of quantitative traits. Principal component regression (PCR) and linear mixed model (LMM) are two commonly used approaches to account for PS in association studies. Previous studies have shown that LMM can be interpreted as including all principal components (PCs) as random-effect covariates
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Application of real-time PCR–based multicolor melting curve with automatic analysis system in pregestational and prenatal thalassemia diagnoses Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-09-28 Xue-Wei Tang, Fan Jiang, Jian Li, Xiao-Mei Lin, Jian-Ying Zhou, Jun-Hui Wan, Lian-Dong Zuo, Yan-Xia Qu, Fa-Tao Li, Gui-Lan Chen, Dong-Zhi Li
To evaluate the value of the real-time PCR–based multicolor melting curve analysis (MMCA) with an automatic analysis system used in a mass thalassemia screening and prenatal diagnosis program.
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Histone modification: Biomarkers and potential therapies in colorectal cancer Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-09-15 Xin An, Xiaohua Lan, Zizhen Feng, Xiaohong Li, Qisheng Su
The complex mechanism of colorectal cancer development is closely associated with epigenetic modifications and is caused by overexpression and/or inactivation of oncogenes. Histone modifying enzymes catalyze histone modifications to alter gene expression, which plays a crucial role in the development and progression of colorectal cancer. Currently, there is more frequent study on histone acetylation
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Genetic architecture of adiposity measures among Asians: Findings from GWAS Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-09-06 Tripti Agarwal, Tanica Lyngdoh, Rajesh Khadgawat, Dorairaj Prabhakaran, Giriraj Ratan Chandak, Gagandeep Kaur Walia
Adiposity has gradually become a global public threat over the years with drastic increase in the attributable deaths and disability adjusted life years (DALYs). Given an increased metabolic risk among Asians as compared to Europeans for any given body mass index (BMI) and considering the differences in genetic architecture between them, the present review aims to summarize the findings from genome-wide
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A novel heterozygous truncating variant in the AGO1 gene in an Iranian family with schizophrenia as an unreported symptom Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-08-17 Atefeh Mir, Erfan Khorram, Yongjun Song, Hane Lee, Mohammad Amin Tabatabaiefar
Intellectual disability (ID) and autism spectrum disorders (ASDs) are the most common developmental disorders in humans. Combined, they affect between 3% and 5% of the population. Although high-throughput genomic methods are rapidly increasing the pool of ASD genes, many cases remain idiopathic. AGO1 is one of the less-known genes related to ID/ASD. This gene encodes a core member protein of the RNA-induced
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Novel GALT variations and genetic spectrum in Turkish population with the correlation of genotype and phenotype Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-08-11 Irem Kalay, Cagri Gulec, Mehmet Cihan Balcı, Guven Toksoy, Gulden Gokcay, Seher Basaran, Mubeccel Demirkol, Zehra Oya Uyguner
Classic galactosemia (OMIM#230400) is an autosomal recessive inborn error of carbohydrate metabolism caused by a deficiency of the galactose-1-phosphate-uridyl-transferase enzyme encoded by the GALT gene. Even though a galactose-restricted diet efficiently resolves the acute complications, it is insufficient to prevent long-term complications regarding speech defects, intellectual functioning, premature
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Reassessing the association of MUC5B with survival in idiopathic pulmonary fibrosis Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-08-03 Siyang Cai, Richard J. Allen, Louise V. Wain, Frank Dudbridge
A variant in the mucin 5B gene (MUC5B) is strongly associated with the risk of idiopathic pulmonary fibrosis. However, the same variant is associated with increased survival time. Previous work suggested that this may be explained by index event bias, with the true effect being to decrease survival. Here, we reassessed this claim using more recent methods and datasets. We found that the statistical
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Functional characterization of a rare pathogenic variant c.875G > A, p.(Cys292Tyr) in COMP Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-07-18 Lan Yin, Yingchuan Zhu, Wenhao Jiang, Yue Song, Yilu Lu, Dachang Tao, Yunqiang Liu, Yongxin Ma
The protein encoded by the cartilage oligomeric matrix protein (COMP) gene is a noncollagenous extracellular matrix (ECM) protein that is important for chondrocyte formation and growth. Variations in the COMP gene cause pseudoachondroplasia (PSACH), which is mainly characterized by short-limbed dwarfing in the clinic.
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Uncovering cilia function in glial development Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-07-10 Rachel M. Bear, Tamara Caspary
Primary cilia play critical roles in regulating signaling pathways that underlie several developmental processes. In the nervous system, cilia are known to regulate signals that guide neuron development. Cilia dysregulation is implicated in neurological diseases, and the underlying mechanisms remain poorly understood. Cilia research has predominantly focused on neurons and has overlooked the diverse
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Pitfalls of predicting age-related traits by polygenic risk scores Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-07-07 Valentina Escott-Price, Karl Michael Schmidt
Polygenic risk scores (PRS) are a method increasingly used to capture the combined effect of genome-wide significant variants and those which individually do not show genome-wide significant association but are likely to contribute to the risk of developing diseases. However, their practical use incurs complications and inconsistencies that so far limit their clinical applicability. The aims of the
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Genetic polymorphism and variability in the Guangdong Hakka, Teochew, and Cantonese groups: A comprehensive analysis of 19 X-STRs Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-06-20 Cheng Xiao, Xingyi Yang, Zhonghao Yu, Weibin Wu, Yuan Wang, Quyi Xu, Ling Chen
X chromosomeshort tandem repeat (X-STR) loci are playing an increasingly important role inforensic work, identifying female traces in male contamination and explainingcomplex kinship analyses.
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Identification of influential rare variants in aggregate testing using random forest importance measures Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-05-23 Rachel Z. Blumhagen, David A. Schwartz, Carl D. Langefeld, Tasha E. Fingerlin
Aggregate tests of rare variants are often employed to identify associated regions compared to sequentially testing each individual variant. When an aggregate test is significant, it is of interest to identify which rare variants are “driving” the association. We recently developed the rare variant influential filtering tool (RIFT) to identify influential rare variants and showed RIFT had higher true
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Association of common BRCA1 variants with predisposition to breast tumors in Pakistan Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-05-16 Ayesha Siddique, Warda Fatima, Naeem Shahid
BRCA1 variants are extensively associated with increased risk of breast cancer. Early detection and screening of variants is still rare in developing countries. Here, we investigated six BRCA1 variants in 300 subjects from Pakistani population using tetra amplification-refractory mutation system (T-ARMS) PCR. Our results indicate significant association of BRCA1 variants rs8176237 (AA; OR 8.2, 95%
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Genetic portrait of the Amazonian communities of Peru and Bolivia: The legacy of the Takanan-speaking people Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-05-10 José R. Sandoval, Susana Revollo, Cinthia Cuellar, Daniela R. Lacerda, Marilza S. Jota, Ricardo Fujita, Fabricio R. Santos
During the colonial period in South America, many autochthonous populations were affected by relocation by European missionary reductions and other factors that impacted and reconfigured their genetic makeup. Presently, the descendants of some “reduced” and other isolated groups are distributed in the Amazonian areas of Peru, Bolivia, and Brazil, and among them, speakers of Takanan and Panoan languages
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Molecular genetic diagnosis of kidney ciliopathies: Lessons from interpreting genomic sequencing data and the requirement for accurate phenotypic data Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-04-12 Sarah Orr, Eric Olinger, Sotia Iosifidou, Miguel Barroso-Gil, Ruxandra Neatu, Katrina Wood, Ian Wilson, , John Andrew Sayer
Introduction: Massively parallel sequencing (MPS) techniques have made a major impact on the identification of the genetic basis of inherited kidney diseases such as the ciliopathy autosomal dominant polycystic kidney disease (ADPKD). Great care must be taken when analysing MPS data in isolation from accurate phenotypic information, as this can cause misdiagnosis. Methods: Here, we describe a family
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The impact of obesity on lung function measurements and respiratory disease: A Mendelian randomization study Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-04-03 Jiayan Liu, Hanfei Xu, L Adrienne Cupples, George T. O’ Connor, Ching-Ti Liu
Observational studies have shown that body mass index (BMI) and waist-to-hip ratio (WHR) are both inversely associated with lung function, as assessed by forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). However, observational data are susceptible to confounding and reverse causation.
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Identification of pathogenic deep intronic variant and exonic LINE-1 insertion in a patient with Meckel syndrome Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-03-27 Sachiko Miyamoto, Kazuyuki Nakamura, Mitsuhiro Kato, Mitsuko Nakashima, Hirotomo Saitsu
Biallelic CC2D2A variants are associated with a wide range of neurodevelopmental disorders including Meckel syndrome. Here we report a Japanese girl with Meckel syndrome harboring a pathogenic deep intronic variant (NM_001378615.1:c.1149+3569A>G) and an exonic LINE-1 insertion, which was predicted to cause aberrant splicing by SpliceAI and was detected by TEMP2 program, respectively. RNA analysis using
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Three siblings with variable degrees of neuromuscular involvement and congenital sideroblastic anemia: A peculiar phenotype and a surprise genotypic explanation Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-03-14 Mai Abd El Salam, Khaled Salama, Yasmeen M. M. Selim, Mariam Saad, Rasha Rady, Salem Alawbathani, Sabine Schroeder, Mohamed A. Elmonem, Nour Elkhateeb
Introduction: Congenital sideroblastic anemias (CSAs) are a group of inherited bone-marrow disorders manifesting with erythroid hyperplasia and ineffective erythropoiesis. Methods: We describe a detailed clinical and genetic characterization of three siblings with CSA. Results: Two of them had limb-girdle myopathy and global developmental delay. The two elder siblings performed allogenic hematopoietic
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A de novo low-frequency mosaic variant of KIF1A causes hereditary spastic paraplegia: A literature review Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-03-10 Mengyuan Liu, Bing Li, Xiaona Wang, Dongxiao Li, Zhenhua Xie, Yuke Li, Yang Gao, Baiyun Chen, Huichun Zhang, Yanli Wang, Chao Gao
The objective of this study was to investigate the pathogenesis and inheritance pattern of a Chinese Han family with hereditary spastic paraplegia and to retrospectively analyze the characteristics of KIF1A gene variants and related clinical manifestations.
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The genetic era of childhood cancer: Identification of high-risk patients and germline sequencing approaches Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-03-10 Oscar Alonso-Luna, Gabriela E Mercado-Celis, Jorge Melendez-Zajgla, Marta Zapata-Tarres, Elvia Mendoza-Caamal
Childhood cancer is a leading cause of death by disease in children ages 5–14, for which there are no preventive strategies. Due to early-age of diagnosis and short period of exposure to environmental factors, increasing evidence suggests childhood cancer could have strong association with germline alterations in predisposition cancer genes but, their frequency and distribution are largely unknown
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Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-03-01
Retraction: Liu, H., Wang, T., Chen, X., Jiang, J., Song, N., Li, R., Xin, Y. and Xuan, S. (2020). Inhibition of miR-499-5p expression improves nonalcoholic fatty liver disease. Annals of Human Genetics. (https://doi.org/10.1111/ahg.12374). The above article, published online on 20 January 2020 in Wiley Online Library (www.wileyonlinelibrary.com), has been retracted by agreement between the journal
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A novel nonsense variant in the ATL3 gene is associated with disturbed pain sensitivity, numbness of distal limbs and muscle weakness Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-03-01 Sanaz Mohammadi, Hossein Jafari Khamirani, Maryam Baneshi, Neda Kamal, Jamal Manoocheri, Mahsa Saffar, Mehdi Dianatpour, Seyed Mohammad Bagher Tabei, Seyed Alireza Dastgheib
Hereditary sensory neuropathy (HSN) describes as a heterogeneous group of peripheral neuropathies. HSN type 1 (HSN1) is one subtype characterized by distal sensory impairment that occurs in the form of numbness, tingling, or pain. To date, only two variants in the atlastin GTPase 3 (ATL3) gene have been identified that result in hereditary sensory neuropathy type 1F (HSN1F) with autosomal dominantinheritance
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Development of molecular diagnostic platform for α0-thalassemia 44.6 kb (Chiang Rai, --CR) deletion in individuals with microcytic red blood cells across Thailand Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-01-29 Pinyaphat Khamphikham, Oravee Hanmanoviriya, Somsakul Pop Wongpalee, Thongperm Munkongdee, Kittiphong Paiboonsukwong, Yupin Jopang, Chaowanee Wangchauy, Charan Sancharernsook, Nathawat Jinorose, Sakorn Pornprasert
The α0-thalassemia 44.6 kb or Chiang Rai (--CR) deletion has been reported in northern Thailand and is capable of causing hemoglobin (Hb) H disease and a lethal α-thalassemia genotype, Hb Bart's hydrops fetalis, in this region. However, there are no current data regarding the frequency of --CR nationwide due to a lack of effective diagnostic assay. Therefore, this study aimed to develop a reliable
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Insights into gene tissue specificity and protein–protein interactions in the context of purifying selection in humans Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-01-27 Massimo Mezzavilla, Massimiliano Cocca
How much are natural selection and gene characteristics, such as the number of protein-protein interactions (PPIs), tissue specificity (𝞽), and expression level, connected?
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Multimarker omnibus tests by leveraging individual marker summary statistics from large biobanks Ann. Hum. Genet. (IF 1.9) Pub Date : 2023-01-22 Angela M. Zigarelli, Hanna M. Venera, Brody A. Receveur, Jack M. Wolf, Jason Westra, Nathan L. Tintle
As biobanks become increasingly popular, access to genotypic and phenotypic data continues to increase in the form of precomputed summary statistics (PCSS). Widespread accessibility of PCSS alleviates many issues related to biobank data, including that of data privacy and confidentiality, as well as high computational costs. However, questions remain about how to maximally leverage PCSS for downstream
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NLRP13 inflammasome complex is hypermethylated in familial Mediterranean fever and global methylation correlates with the disease severity Ann. Hum. Genet. (IF 1.9) Pub Date : 2022-12-30 Feyzanur Yildirimtepe Caldiran, Koksal Deveci, Ercan Cacan
Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by variations in the MEFV gene, which encodes the pyrin protein, a member of the inflammasomes. Despite the complex pathogenesis of FMF, epigenetic changes also play roles in the disease progression. In our previous study, we observed a relationship between NLRP13, which is one of the members of the inflammasome complex and has
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High diagnostic yield of targeted next-generation sequencing panel as a first-tier molecular test for the patients with myopathy or muscular dystrophy Ann. Hum. Genet. (IF 1.9) Pub Date : 2022-12-27 Büşranur Çavdarlı, Özlem Yayici Köken, Saide Betül Arslan Satılmış, Şule Bilen, Didem Ardıçlı, Ahmet Cevdet Ceylan, Cavidan Nur Semerci Gündüz, Haluk Topaloğlu
Muscular dystrophies are a heterogeneous group of neuromuscular disorders with a wide range of the clinical and genetic spectrum. Whole-exome sequencing (WES) has been on the rise to become the usual method of choice for molecular diagnosis in patients presenting with muscular dystrophy or congenital or metabolic myopathy phenotype. Here, we used a panel with 47 genes including not only muscular dystrophy
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Estimation of genetic heritabilities of human traits in case–control studies Ann. Hum. Genet. (IF 1.9) Pub Date : 2022-12-23 Die Hu, Shuyue Chen, Hong Zhang
It is of great interest to detect missing heritability for human complex traits. Additive genetic effects (ADD), maternal genetic effects (MGE), and parent-of-origin effects (POE) play important roles in genetic mechanisms. Methods have been developed in the literature to analyze heritabilities due to ADD, POE, and MGE separately but not simultaneously. In this paper, a new model termed APM is proposed
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Identification of key variants correlated with susceptibility of primary osteoporosis in the Chinese Han group Ann. Hum. Genet. (IF 1.9) Pub Date : 2022-12-08 Yanjiao Li, Qi Liu, Qiuye Ma, Zhaoxia Ma, Juan Chen, An Yu, Changguo Ma, Lihua Qiu, Hong Shi, Hongsuo Liang, Min Hu
Primary osteoporosis is a systemic skeletal disease characterized by reduced bone mass and vulnerability to fractures. The genetics of osteoporosis in the Chinese population remain unclear, which hinders the prevention and treatment of osteoporosis in China. This study aimed to explore the susceptibility genes and the roles played by their variants in osteoporosis.
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The role of next-generation sequencing in the examination of signaling genes in Brca1/2-negative breast cancer cases Ann. Hum. Genet. (IF 1.9) Pub Date : 2022-12-07 Naci Cine, Cansu Ugurtas, Merve Gokbayrak, Duygu Aydin, Gulhan Demir, Seda Kuru, Deniz Sunnetci-Akkoyunlu, Seda Eren-Keskin, Turgay Simsek, Devrim Cabuk, Maksut Gorkem Aksu, Nuh Zafer Canturk, Hakan Savli
Breast cancer is the most prevalent malignancy in women worldwide. Although pathogenic variants in the BRCA1/2 genes are responsible for the majority of hereditary breast cancer cases, a substantial proportion of patients are negative for pathogenic variations in these genes. In cancers, the signal transduction pathways of the cell are usually affected first. Therefore, this study aimed to detect and
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The expression of NOTUM in replantation of severed fingers may be an important treatment factor Ann. Hum. Genet. (IF 1.9) Pub Date : 2022-12-05 Bin Li, Libing Xiao, Danhong Ye, Siyi Zhong, Qiaoyu Yan
After years of development, digital replantation has become a mature treatment. Although the NOTUM gene has been shown to be involved in the formation of vertebrate nerves, whether it contributes to the osteogenic mechanism of severed finger replantation remains unknown. In response to this, this study investigates the specific details of NOTUM involvement in replantation of severed fingers.
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Proteome changes in autosomal recessive primary microcephaly Ann. Hum. Genet. (IF 1.9) Pub Date : 2022-11-29 Sami Zaqout, Atef Mannaa, Oliver Klein, Angelika Krajewski, Joachim Klose, Lena Luise-Becker, Ahmed Elsabagh, Khaled Ferih, Nadine Kraemer, Ethiraj Ravindran, Konstantin Makridis, Angela M. Kaindl
: Autosomal recessive primary microcephaly (MCPH) is a rare and genetically heterogeneous group of disorders characterized by intellectual disability and microcephaly at birth, classically without further organ involvement. MCPH3 is caused by biallelic variants in the cyclin-dependent kinase 5 regulatory subunit-associated protein 2 gene CDK5RAP2. In the corresponding Cdk5rap2 mutant or Hertwig's anemia
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High accuracy of single-molecule real-time sequencing in detecting a rare α-globin fusion gene in carrier screening population Ann. Hum. Genet. (IF 1.9) Pub Date : 2022-11-01 Qiao-Miao Zhou, Fan Jiang, Jing Xu, Dan Lin, Ren-Liang Huang, Jian-Ying Zhou, Yan-Xia Qu, Dong-Zhi Li
The α-globin fusion gene between the HBA2 and HBAP1 genes becomes clinically important in thalassemia screening because this fusion gene can cause severe hemoglobin (Hb) H disease when combining with α0-thalassemia (α0-thal). Due to its uncommon rearrangement in the α gene cluster without dosage changes, this fusion gene is undetectable by common molecular testing approaches used for α-thal diagnosis
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Segregation analysis identifies specific alpha-defensin (DEFA1A3) SNP–CNV haplotypes in predisposition to IgA nephropathy Ann. Hum. Genet. (IF 1.9) Pub Date : 2022-10-10 Nzar A. A. Shwan, Eric C. Moise, Paula E. Necsoiu, Amy J. Farr, Daniel P. Gale, Jonathan Barratt, John A. L. Armour
Immunoglobulin A (IgA) nephropathy is a disorder of the immune system affecting kidney function, and genome-wide association studies (GWAS) have defined numerous loci with associated variation, all implicating components of innate or adaptive immunity. Among these, single nucleotide polymorphisms (SNPs) in a region including the multiallelic copy number variation (CNV) of DEFA1A3 are associated with
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Germline variants screening of MLH1, MSH2, MSH6 and PMS2 genes in 64 Algerian Lynch syndrome families: The first nationwide study Ann. Hum. Genet. (IF 1.9) Pub Date : 2022-09-08 Asma-Lamia Boumehdi, Farid Cherbal, Feriel Khider, Mohammed Oukkal, Hassen Mahfouf, Ferhat Zebboudj, Mustapha Maaoui
Colorectal cancer is the second leading cause of cancer-related deaths in women and men in Algeria. Lynch syndrome (LS) is an autosomal dominant disease caused by heterozygous germline pathogenic variants in mismatch repair genes (MMR) and frequently predisposes to colorectal cancer. However, data about MMR germline pathogenic variants in Algerian patients are limited. This first nationwide study aims
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Study of variants in genes implicated in rare familial migraine syndromes and their association with migraine in 200,000 exome-sequenced UK Biobank participants Ann. Hum. Genet. (IF 1.9) Pub Date : 2022-08-31 Katherine Alexis Markel, David Curtis
A number of genes have been implicated in rare familial syndromes which have migraine as part of their phenotype but these genes have not previously been implicated in the common form of migraine.