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Pharmacological Treatment of Severe Breathing Abnormalities in a Case of HNRNPU Epileptic Encephalopathy Mol. Syndromol. (IF 1.198) Pub Date : 2021-01-11 Carlotta Spagnoli; Susanna Rizzi; Grazia Gabriella Salerno; Daniele Frattini; Juha Koskenvuo; Carlo Fusco
Abnormal breathing patterns are a typical feature of Rett and Pitt-Hopkins syndrome and their variants. Their treatment can be challenging, with a risk of long-term detrimental consequences. Early infantile epileptic encephalopathy (EIEE) type 54 is a rare epileptic encephalopathy caused by pathogenic variants in the heterogeneous nuclear ribonucleoprotein U (HNRNPU) gene. Only one case has been described
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The Role of Copy Number Variations and FHIT Gene on Phenotypic Characteristics of Cases Diagnosed with Autism Spectrum Disorder Mol. Syndromol. (IF 1.198) Pub Date : 2020-12-16 Gül Ünsel Bolat; Hilmi Bolat
Copy number variations (CNVs) have been implied in the etiology of autism spectrum disorder (ASD), and microarray-based techniques are performed as a first-step genetic test. Our aim was to present clinical features and CNV profiles of patients with ASD and their parents. Array-CGH was applied to detect CNVs. Previously as likely pathogenic reported duplications were detected at 16p13.11 and 11p15
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Prenatal Diagnosis of Acromelic Frontonasal Dysostosis Mol. Syndromol. (IF 1.198) Pub Date : 2020-12-15 Cristina Martínez-Payo; Fe Amalia García-Santiago; Karen E. Heath; Eduardo Gavin; Elena Mansilla-Aparicio
Acromelic frontonasal dysostosis (AFND; MIM #603671) is a rare autosomal dominant genetic disorder caused by a heterozygous mutation in the ZSWIM6 (KIAA1577) gene located at chromosome 5q12.1. It is phenotypically characterized by frontonasal malformation with hypertelorism, telecanthus, nasal clefting or bifid nasal tip, wide fontanels and sutures, brachycephaly, and cleft palate. The patients also
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Language Impairment with a Partial Duplication of DOCK8 Mol. Syndromol. (IF 1.198) Pub Date : 2020-12-11 Antonio Benítez-Burraco; Maite Fernández-Urquiza; Mª Salud Jiménez-Romero
Duplications of the distal region of the short arm of chromosome 9 are rare, but are associated with learning disabilities and behavioral disturbances. We report in detail the cognitive and language features of a child with a duplication in the 9p24.3 region, arr[hg19] 9p24.3(266,045–459,076)×3. The proband exhibits marked expressive and receptive problems, which affect both structural and functional
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Dystonia and Contractures are Potential Early Signs of CACNA1E-Related Epileptic Encephalopathy Mol. Syndromol. (IF 1.198) Pub Date : 2020-12-10 Nelmar V. Ortiz Cabrera; Anna Duat Rodríguez; Bárbara Fernández Garoz; Beatriz Bernardino Cuesta; María Jiménez Legido; Verónica Cantarín Extremera; Juan J. García Peñas
Epileptic encephalopathy related to CACNA1E has been described as a severe neurodevelopmental disorder presenting with early-onset refractory seizures, hypotonia, macrocephaly, hyperkinetic movements, and contractures and is associated with an autosomal dominant inheritance pattern. Most pathogenic variants described to date are missense variants with a gain of function effect, and the role of haploinsufficiency
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Expanding the Phenotype of TUBB2A-Related Tubulinopathy: Three Cases of a Novel, Heterozygous TUBB2A Pathogenic Variant p.Gly98Arg Mol. Syndromol. (IF 1.198) Pub Date : 2020-12-09 Lindsey Schmidt; Karen E. Wain; Catherine Hajek; Juvianee I. Estrada-Veras; Maria J. Guillen Sacoto; Ingrid M. Wentzensen; Alka Malhotra; Amanda Clause; Denise Perry; Andres Moreno-De-Luca; Megan Bell
Tubulinopathies are a group of conditions caused by variants in 6 tubulin genes that present with a spectrum of brain malformations. One of these conditions is TUBB2A-related tubulinopathy. Currently, there are 9 reported individuals with pathogenic variants within the TUBB2A gene, with common manifestations including, but not limited to, global developmental delay, seizures, cortical dysplasia, and
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Chromothripsis and Duplications as Underappreciated Genomic Gremlins Mol. Syndromol. (IF 1.198) Pub Date : 2020-12-07 Martin Poot
Mol Syndromol
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A Frameshift Variant in KIAA0825 Causes Postaxial Polydactyly Mol. Syndromol. (IF 1.198) Pub Date : 2020-12-03 Muhammad Bilal; Wasim Ahmad
Postaxial polydactyly (PAP) is characterized by counterproductive 5th digit (pinky finger) duplication on hands and/or feet which often leads to functional complications. To date, at least 11 genes involved in causing various types of nonsyndromic polydactylies have been reported. In the present study, a consanguineous family of Sindhi origin with a segregating nonsyndromic form of PAP in an autosomal
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Wiedemann-Steiner Syndrome as a Differential Diagnosis of Cornelia de Lange Syndrome Using Targeted Next-Generation Sequencing: A Case Report Mol. Syndromol. (IF 1.198) Pub Date : 2020-12-01 Selma Demir; Hakan Gürkan; Veysel Öz; Sinem Yalçıntepe; Emine İ. Atlı; Engin Atlı
Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant disorder with a variable clinical phenotype including synophrys, hypertelorism, thick eyebrows, long eyelashes, wide nasal bridge, long philtrum, hypertrichosis, growth retardation, and intellectual disability. Cornelia de Lange syndrome (CdLS) is a rare disease characterized by synophrys, long eyelashes, limb abnormalities, generalized
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Novel Findings in Floating-Harbor Syndrome and a Mini-Review of the Literature Mol. Syndromol. (IF 1.198) Pub Date : 2020-11-30 Pelin Ercoskun; Cigdem Yuce-Kahraman
Floating-Harbor syndrome (FHS) is a rare autosomal dominant genetic disorder characterized by proportionate short stature with delayed bone maturation, lack of expressive language, and distinctive facial features including a large nose, long eyelashes, deeply set eyes, and triangular face. Mutations in the SRCAP gene cause truncated SNF2-related CREBBP activator protein (SRCAP) and lead to FHS. SRCAP
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Clinical and Molecular Spectrum of Four Patients Diagnosed with Mowat-Wilson Syndrome Mol. Syndromol. (IF 1.198) Pub Date : 2020-11-20 Durdugul Ayyildiz Emecen; Esra Isik; Gulen E. Utine; Pelin O. Simsek-Kiper; Tahir Atik; Ferda Ozkinay
Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by distinctive facial features, congenital heart defects, Hirschsprung disease, genitourinary anomalies, various structural brain anomalies, and intellectual disability. Pathogenic mutations that result in haploinsufficiency in the ZEB2 gene cause MWS. In this study, we aimed to evaluate the clinical features and molecular
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Phenotypic Characteristics and Copy Number Variants in a Cohort of Colombian Patients with VACTERL Association Mol. Syndromol. (IF 1.198) Pub Date : 2020-11-11 Olga M. Moreno; Ana I. Sánchez; Angélica Herreño; Gustavo Giraldo; Fernando Suárez; Juan Carlos Prieto; Ana Shaia Clavijo; Mercedes Olaya; Yaris Vargas; Javier Benítez; Jordi Surallés; Adriana Rojas
VACTERL association (OMIM 192350) is a heterogeneous clinical condition characterized by congenital structural defects that include at least 3 of the following features: vertebral abnormalities, anal atresia, heart defects, tracheoesophageal fistula, renal malformations, and limb defects. The nonrandom occurrence of these malformations and some familial cases suggest a possible association with genetic
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A Case of UDP-Galactose 4′-Epimerase Deficiency Associated with Dyshematopoiesis and Atrioventricular Valve Malformations: An Exceptional Clinical Phenotype Explained by Altered N-Glycosylation with Relative Preservation of the Leloir Pathway Mol. Syndromol. (IF 1.198) Pub Date : 2020-10-29 Christopher A. Febres-Aldana; Liset Pelaez; Meredith S. Wright; Ossama M. Maher; Anthony J. Febres-Aldana; Jun Sasaki; Parul Jayakar; Anuj Jayakar; Magaly Diaz-Barbosa; Michelin Janvier; Bala Totapally; Daria Salyakina; Jorge R. Galvez-Silva
The generalized form of UDP-galactose-4′-epimerase (GALE) deficiency causes hypotonia, failure to thrive, cataracts, and liver failure. Individuals with non-generalized forms may remain asymptomatic with uncertain long-term outcomes. We report a 2-year-old child compound heterozygous for GALE p.R51W/p.G237D who never developed symptoms of classic galactosemia but has a history of congenital combined
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Fanconi Anemia: A Syndrome of Anemia and Skeletal Malformations Progressing to a Gene Network Involved in Genomic Stability and Malignant Disease Mol. Syndromol. (IF 1.198) Pub Date : 2020-10-22 Martin Poot
Mol Syndromol
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Publisher's Note Mol. Syndromol. (IF 1.198) Pub Date : 2020-10-19 Lisa G. Shaffer; Martin Poot; Lisa G. Shaffer; Michael Schmid; Judith A. Hartz; Mechthild Büche; Karin Schmid; Tanja Gösswein; Martina Guttenbach; Claus Steinlein; Yanick Crow; Miikka Vikkula; Jill Rosenfeld Mokry; Christopher Cunniff; Maki Fukami; Ben Solomon; Martin Poot; Kenjiro Kosaki; Geert Mortier; Maximilian Muenke; Marco Tartaglia; Arthur S. Aylsworth; Carl Ernst; Barbara Vona; Seema Lalani;
Mol Syndromol
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A Novel ELP2 Compound Heterozygous Mutation in a Boy with Severe Intellectual Disability, Spastic Diplegia, Stereotypic Behavior and Review of the Current Literature Mol. Syndromol. (IF 1.198) Pub Date : 2020-10-15 Ayberk Turkyilmaz; Gunes Sager
The elongator complex consists of 6 highly conserved subunit proteins and is indispensable for various cellular functions, such as transcription elongation, histone acetylation, and tRNA modification. The elongator complex contains 2 subunits, each of which consists of 3 different proteins (encoded by the ELP1–3 and ELP4–6 genes). According to the OMIM database, ELP2 gene variations have been reported
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Application of Chromosome Microarray Analysis in the Investigation of Developmental Disabilities and Congenital Anomalies: Single Center Experience and Review of NRXN3 and NEDD4L Deletions Mol. Syndromol. (IF 1.198) Pub Date : 2020-10-05 Alper Han Çebi; Şule Altıner
Chromosomal microarray analysis (CMA) is a first step test used for the diagnosis of patients with developmental delay, intellectual disability, autistic spectrum disorder, and multiple congenital anomalies. Its widespread usage has allowed genome-wide identification of copy number variations (CNVs). In our study, we performed a retrospective study on clinical and microarray data of 237 patients with
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Eyes See what the Mind Knows: Clues to Pattern Recognition in Single Enzyme Deficiency-Related Peroxisomal Disorders Mol. Syndromol. (IF 1.198) Pub Date : 2020-09-30 Veronica Arora; Sunita Bijarnia-Mahay; Sudhisha Dubey; Renu Saxena
Peroxisomal disorders are a heterogeneous group of inborn errors of metabolism that result in impaired function of the peroxisome. Within this, single enzyme deficiencies are known to cause a constellation of symptoms not very different from the peroxisome biogenesis defects. Thus, there is a need to identify features that differentiate the two. We present 3 molecularly confirmed families: 1 with Acyl
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Phenotypic and Molecular Cytogenetic Analysis of a Case of Monosomy 1p36 Syndrome due to Unbalanced Translocation Mol. Syndromol. (IF 1.198) Pub Date : 2020-09-23 Dalia F. Hussen; Alaa K. Kamel; Mona K. Mekkawy; Engy A. Ashaat; Mona O. El Ruby
Monosomy 1p36 syndrome is one of the most common submicroscopic deletion syndromes, which is characterized by the presence of delayed developmental milestones, intellectual disability, and clinically recognizable dysmorphic craniofacial features. The syndrome comprises 4 cytogenetic groups including pure terminal deletions, interstitial deletions, complex rearrangements, and derivative chromosomes
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Clinical and Molecular Characterization of Fanconi Anemia Patients in Turkey Mol. Syndromol. (IF 1.198) Pub Date : 2020-09-23 Güven Toksoy; Dilek Uludağ Alkaya; Gülendam Bagirova; Şahin Avcı; Agharza Aghayev; Nilay Günes; Umut Altunoğlu; Yasemin Alanay; Seher Başaran; Ezgi G. Berkay; Birsen Karaman; Tiraje T. Celkan; Hilmi Apak; Hülya Kayserili; Beyhan Tüysüz; Zehra O. Uyguner
Fanconi anemia (FA) is a rare multigenic chromosomal instability syndrome that predisposes patients to life-threatening bone marrow failure, congenital malformations, and cancer. Functional loss of interstrand cross-link (ICL) DNA repair system is held responsible, though the mechanism is not yet fully understood. The clinical and molecular findings of 20 distinct FA cases, ages ranging from perinatal
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A Deep Intronic Variant Activates a Pseudoexon in the MTM1Gene in a Family with X-Linked Myotubular Myopathy Mol. Syndromol. (IF 1.198) Pub Date : 2020-09-16 Jamie Fitzgerald; Cori Feist; Paula Dietz; Stephen Moore; Donald Basel
We report a novel intronic variant in the MTM1 gene in 4 males in a family with severe X-linked myotubular myopathy. The A#x3e;G variant in deep intronic space activates a cryptic 5′ donor splice site resulting in the inclusion of a 48-bp pseudoexon into the mature MTM1 mRNA. The variant is present in all affected males, absent in unaffected males, and heterozygous in the mother of the affected males
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Hyperinsulinemic Hypoglycemia in a Patient with Costello Syndrome: An Etiology to Consider in Hypoglycemia Mol. Syndromol. (IF 1.198) Pub Date : 2020-09-16 Dogus Vuralli; Can Kosukcu; Ekim Taskiran; Pelin Ozlem Simsek-Kiper; Gulen Eda Utine; Koray Boduroglu; Ayfer Alikasifoglu; Mehmet Alikasifoglu
Several endocrine disorders have been defined in patients with Costello syndrome (CS). In this report, we describe a patient with CS accompanied by a clinical picture of hyperinsulinemic hypoglycemia responsive to diazoxide treatment. A 41-day-old female patient with a birth weight of 3,600 g was referred for atypical facial features and swallowing dysfunction. She had a weight of 4,000 g (−0.8 SDS)
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First Infertile Case with CSTF2TGene Mutation Mol. Syndromol. (IF 1.198) Pub Date : 2020-09-14 Ozlem Gorukmez; Orhan Gorukmez
Male infertility is multifactorial and presents with heterogeneous phenotypic features. Genetic factors are responsible for up to 15% of the male infertility cases. Loss of the Cstf2t gene in male mice results in infertility. No disease-associated mutations have been described for this gene in infertile men. Here, we report a patient diagnosed with infertility in whom a homozygous nonsense mutation
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A Case of Ring Chromosome 18 with Single Umbilical Artery Detected During Prenatal Period Mol. Syndromol. (IF 1.198) Pub Date : 2020-09-10 Nazan Eras
Fetuses with a single umbilical artery have a risk of increased chromosomal anomalies and congenital malformations. Ring chromosomes are rare and the phenotypic and clinical characteristics of affected individuals show great variability depending on the quantity of the lost critical genes or gains during the formation of the ring or due to mitotic instability. Ring chromosome 18 [r(18)] is characterized
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Molecular Etiology of Isolated Congenital Cataract Using Next-Generation Sequencing: Single Center Exome Sequencing Data from Turkey Mol. Syndromol. (IF 1.198) Pub Date : 2020-09-09 Hande Taylan Sekeroglu; Beren Karaosmanoglu; Ekim Z. Taskiran; Pelin O. Simsek Kiper; Mehmet Alikasifoglu; Koray Boduroglu; Turgay Coskun; Gulen Eda Utine
Congenital cataract, which refers to lenticular opacity diagnosed at birth or more commonly during the first year of life, is one of the leading causes of childhood blindness. Molecular understanding of the disease pathogenesis has evolved thanks to many studies based on modern technologies. In this study, we aimed to identify and discuss the molecular etiology of nonsyndromic or nonmetabolic bilateral
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Intrauterine Growth Restriction and Hypertrophic Cardiomyopathy as Prenatal Ultrasound Findings in a Case of Leprechaunism Mol. Syndromol. (IF 1.198) Pub Date : 2020-09-02 Kevin Perge; Mona Massoud; Hélène Gauthier-Moulinier; Olivier Lascols; Nicolas Pangaud; Carine Villanueva; Linda Pons
Donohue syndrome (leprechaunism; OMIM *246200) is a rare and often lethal autosomal recessive disease caused by mutations in the INSR gene. We report the case of a 29-year-old pregnant woman, primigravida, who was referred at 33 weeks of gestation for severe intrauterine growth restriction (IUGR). Ultrasound examination found severe IUGR associated with an obstructive hypertrophic cardiomyopathy (HCM)
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Clonazepam as an Effective Treatment for Epilepsy in a Female Patient with NEXMIF Mutation: Case Report Mol. Syndromol. (IF 1.198) Pub Date : 2020-09-01 Masashi Ogasawara; Eiji Nakagawa; Eri Takeshita; Kohei Hamanaka; Satoko Miyatake; Naomichi Matsumoto; Masayuki Sasaki
The NEXMIF (KIAA2022) gene is located in the X chromosome, and hemizygous mutations in NEXMIF cause X-linked intellectual disability in male patients. Female patients with heterozygous mutations in NEXMIF also show similar, but milder, intellectual disability. Most female patients demonstrate intractable epilepsy compared with male patients, and the treatment strategy for epilepsy is still uncertain
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3-Hydroxyisobutyryl-CoA Hydrolase Deficiency in a Turkish Child with a Novel HIBCH Gene Mutation and Literature Review Mol. Syndromol. (IF 1.198) Pub Date : 2020-06-16 Mustafa Kılıç; Fatma Kurt-Çolak
3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency (OMIM 250620) is an autosomal recessive inborn error of valine catabolism characterized by severely delayed psychomotor development, progressive neurodegeneration, recurrent metabolic attacks with intercurrent illness, increased lactic acid, cerebral atrophy, and brain lesions in the basal ganglia. HIBCH gene defect is a very rare organic aciduria
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A Novel de novo Frameshift Mutation in the BCL11A Gene in a Patient with Intellectual Disability Syndrome and Epilepsy. Mol. Syndromol. (IF 1.198) Pub Date : 2020-06-13 Georg Christoph Korenke,Björn Schulte,Saskia Biskup,John Neidhardt,Marta Owczarek-Lipska
Intellectual disability syndrome (IDS) associated with a hereditary persistence of fetal haemoglobin (HbF), also known as Dias-Logan syndrome, is commonly characterised by psychomotor developmental delay, intelectual disability, language delay, strabismus, thin upper lip, abnormalities of external ears, microcephaly, downslanting palpebral fissures. Sporadically, autism spectrum disorders and blue
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Coffin-Siris Syndrome 4-Related Spectrum in a Young Woman Caused by a Heterozygous SMARCA4 Deletion Detected by High-Resolution aCGH. Mol. Syndromol. (IF 1.198) Pub Date : 2020-06-13 Anastasios Mitrakos,Leandros Lazaros,Amelia Pantou,Ariadni Mavrou,Emmanuel Kanavakis,Maria Tzetis
Coffin-Siris Syndrome 4 is an autosomal dominant congenital malformation syndrome caused by heterozygous mutations in the SMARCA4 gene with its main features being intellectual disability, developmental delay, behavioral abnormalities, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Here, we report a young woman with developmental delay, moderate intellectual disability, and
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Distal 3p Duplication and 22q13.3 Deletion with Severe Hypotonia Originating from a Paternal Balanced Translocation (3;22) Mol. Syndromol. (IF 1.198) Pub Date : 2020-06-10 Sinem Yalcintepe; Emine I. Atli; Engin Atli; Selma Demir; Nukhet A. Ciftdemir; Ridvan Duran; Janset Ozdemir; Hakan Gurkan
In this study, we present a case with distal 3p duplication and 22q13.3 deletion due to unbalanced meiotic segregation in her father carrying a balanced translocation. The 2-month-old girl was examined for her severe hypotonia, developmental delay, and mild dysmorphic appearance. Clinical features include broad forehead, hypertelorism, laterally extended eyebrows, long eyelashes, a depressed nasal
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Intrafamilial Variability in LPIN1-Related Rhabdomyolysis Mol. Syndromol. (IF 1.198) Pub Date : 2020-05-27 Linda Pons; Cécile Acquaviva-Bourdain; Sonia Teyssedre; Capucine Didier; Alice Veauville; Julie Steffann; Stéphanie Gobin; Pascale de Lonlay; Nathalie Guffon; Alain Fouilhoux
LPIN1 molecular alterations were identified as a major cause of severe recurrent rhabdomyolysis. The prognosis is poor, with a third of patients dying from cardiac arrest during an acute episode. We describe herein a familial case of a young boy and his mother both affected by the same homozygous LPIN1 mutation. The index case experienced a first extremely severe episode of rhabdomyolysis at 14 months
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How Many Genes Does It Take? Mol. Syndromol. (IF 1.198) Pub Date : 2020-04-22 Martin Poot
Mol Syndromol 2020;11:59-61
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Renpenning Syndrome in a Turkish Patient: de novo Variant c.607C>T in PACS1 and Hypogammaglobulinemia Phenotype. Mol. Syndromol. (IF 1.198) Pub Date : 2020-04-17 Fatma Kurt Colak,Nilnur Eyerci,Caner Aytekin,Ayse S Eksioglu
Renpenning syndrome is an X-linked intellectual disability syndrome caused by mutations in the human polyglutamine binding protein 1 (PQBP1) gene characterized by intellectual disability (ID), microcephaly, and dysmorphic facial features. We report a Turkish child with a novel pathogenic variant in PQBP1 and a likely pathogenic variant in the PACS1 gene presenting with growth restriction, microcephaly
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Proximal Deletion 12q with a New Insight to Growth Retardation Mol. Syndromol. (IF 1.198) Pub Date : 2020-04-10 Maria Sobol; Ann-Charlotte Thuresson; Nathalie Palmberg; Cecilia Soussi Zander
Proximal deletion of the long arm of chromosome 12 is a rare chromosomal abnormality described in about 20 patients. Known deletions span the region from 12q11 to 12q13 and include the genes YAF2, AMIGO2, and NELL2. These are suggested as candidate genes for the key phenotypic features such as growth and psychomotor retardation. Here, we present a case with a 3.1-Mb interstitial deletion at 12q12q13
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Seizures and Cardiomyopathy in a Patient with Pallister-Killian Syndrome due to Hexasomy 12p Mosaicism. Mol. Syndromol. (IF 1.198) Pub Date : 2020-04-10 Reha M Toydemir,Emanuele Panza,Maria C Longhurst,Sarah T South,Alan F Rope
Pallister-Killian syndrome (PKS) is a rare disorder presenting with developmental delay, numerous dysmorphic features, and skin pigmentation anomalies. It is caused by mosaic tetrasomy of the short arm of chromosome 12. In most instances, tetrasomy is due to a supernumerary isochromosome i(12)(p10). Although mitotic instability is a generally accepted behavior for supernumerary chromosomes, hexasomy
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22q13 Microduplication Syndrome in Siblings with Mild Clinical Phenotype: Broadening the Clinical and Behavioral Spectrum. Mol. Syndromol. (IF 1.198) Pub Date : 2020-04-04 Anikó Ujfalusi,Orsolya Nagy,Beáta Bessenyei,Györgyi Lente,Irén Kántor,Ádám J Borbély,Katalin Szakszon
Distal duplication 22q (22q13.3qter) is a rare condition with only 24 cases described so far. Parental balanced reciprocal translocations and pericentric inversions involving chromosome 22 predispose to the conception of an unbalanced offspring and are more frequently reported than de novo events. The clinical phenotype of patients is highly variable and does not necessarily correlate with the extent
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Three Offspring with Cri-du-Chat Syndrome from Phenotypically Normal Parents. Mol. Syndromol. (IF 1.198) Pub Date : 2020-04-02 Dilek U Alkaya,Birsen Karaman,Beyhan Tüysüz
Cri-du-chat syndrome is characterized by facial dysmorphism, intellectual disability, and multiple congenital anomalies. Most cases occur de novo. Here, we report 3 siblings with cri-du-chat syndrome born to healthy parents. The proband was admitted to our clinic at the age of 6.5 years due to severe intellectual disability, facial dysmorphism, and heart defect. His karyotype showed a deletion of chromosome
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New Compound Heterozygous Splice Site Mutations of the Skeletal Muscle Ryanodine Receptor (RYR1) Gene Manifest Fetal Akinesia: A Linkage with Congenital Myopathies. Mol. Syndromol. (IF 1.198) Pub Date : 2020-04-01 Nebojsa Zecevic,Vladimir Arsenijevic,Emmanouil Manolakos,Ioannis Papoulidis,Georgios Theocharis,Anastasios Sartsidis,Tryfon Tsagas,Ioannis Tziotis,Themistoklis Dagklis,Georgios Kalogeros,Ioannis Tsakiridis,Milica Filipovic Stankovic,Makarios Eleftheriades
Mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been linked to malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. RYR1 is an intracellular calcium release channel and plays a crucial role in the sarcoplasmic reticulum and transverse tubule connection. Here, we report 2 fetuses from the same parents with compound heterozygous
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Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus. Mol. Syndromol. (IF 1.198) Pub Date : 2020-03-28 Ji-Shi Liu,Hao Huang,Jie-Yuan Jin,Ran Du,Chen-Yu Wang,Liang-Liang Fan
Loss of function of arginine vasopressin receptor 2 (AVPR2) may affect the recognition and binding of arginine vasopressin (AVP) which, in turn, may prevent the activation of Gs/adenylate cyclase and reduce the reabsorption of water by renal tubules and combined tubes. Finally, the organism may suffer from nephrogenic diabetes insipidus (NDI), a kind of kidney disorder featured by polyuria and polydipsia
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Diagnosis of Bloom Syndrome in a Patient with Short Stature, Recurrence of Malignant Lymphoma, and Consanguineous Origin. Mol. Syndromol. (IF 1.198) Pub Date : 2020-03-21 Jakub Trizuljak,Terezie Petruchová,Ivona Blaháková,Zuzana Vrzalová,Věra Hořínová,Martina Doubková,Jozef Michalka,Jiří Mayer,Šárka Pospíšilová,Michael Doubek
Bloom syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early-onset cancer and development of multiple malignancies. Loss-of-function variants of the BLM gene, which codes for a RecQ helicase, cause Bloom syndrome. We report a consanguineous family
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Two Novel Variants and One Previously Reported Variant in the Insulin Receptor Gene in Two Cases with Severe Insulin Resistance Syndrome. Mol. Syndromol. (IF 1.198) Pub Date : 2020-03-18 Aydilek Dagdeviren Cakir,Said Saidov,Hande Turan,Serdar Ceylaner,Yavuz Özer,Tufan Kutlu,Oya Ercan,Olcay Evliyaoglu
Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS) are rare diseases caused by biallelic variants within the insulin receptor gene (INSR). Here, we report 2 cases: one with DS and the other with RMS. The case with DS presented with intrauterine growth retardation, nipple hypertrophy, clitoromegaly, distended abdomen, hypertrichosis, and dysmorphic features. The second case showed severe acanthosis
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Whole-Exome Sequencing Identifies Three Candidate Homozygous Variants in a Consanguineous Iranian Family with Autism Spectrum Disorder and Skeletal Problems. Mol. Syndromol. (IF 1.198) Pub Date : 2020-03-11 Saeed Farajzadeh Valilou,Afagh Alavi,Mahdiyeh Pashaei,Saghar Ghasemi Firouzabadi,Yousef Shafeghati,Ahoura Nozari,Fatemeh Hadipour,Zahra Hadipour,Bijan Maghsoodlou Estrabadi,Seyed Gholamreza Noorazar,Susan Banihashemi,Javad Karimian,Mahshid Fattahi,Farkhondeh Behjati
Autism spectrum disorder (ASD) is characterized by 3 core symptoms with impaired social communication, repetitive behavior, and/or restricted interests in early childhood. As a complex neurodevelopmental disorder (NDD), the phenotype and severity of autism are extremely heterogeneous. Genetic factors have a key role in the etiology of autism. In this study, we investigated an Azeri Turkish family with
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Novel Clinical and Radiological Findings in a Family with Autosomal Recessive Omodysplasia. Mol. Syndromol. (IF 1.198) Pub Date : 2020-03-07 Allan Bayat,Morton Dunø,Maria Kirchhoff,Finn S Jørgensen,Gen Nishimura,Hanne B Hove
Autosomal recessive omodysplasia (GPC6-related) is a rare short-limb skeletal dysplasia caused by biallelic mutations in the GPC6 gene. Affected individuals manifest with rhizomelic short stature, decreased mobility of elbow and knee joints as well as craniofacial anomalies. Both upper and lower limbs are severely affected. These manifestations contrast with normal height and limb shortening restricted
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A Novel COL3A1 c.2644G>T; p.(Gly882Cys) Variant in a Turkish Family with Vascular Ehlers-Danlos Syndrome. Mol. Syndromol. (IF 1.198) Pub Date : 2020-02-28 Ömer Aydıner,Veysel S Hançer
Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant disease, also known as EDS type IV. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000 with EDS type IV representing approximately 5-10% of the cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. vEDS diagnosis is a challenging process.
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Interstitial 4q Deletion Syndrome Including NR3C2 Causing Pseudohypoaldosteronism. Mol. Syndromol. (IF 1.198) Pub Date : 2019-12-21 Amanda Barone Pritchard,Alyssa Ritter,Hutton M Kearney,Kosuke Izumi
Interstitial and terminal deletions of chromosome 4q have been described for many years and have variable phenotypes depending on the size of the deletion present. Clinical features can include developmental delay, growth difficulty, digital differences, dysmorphic features, and cardiac anomalies. Here, we present an infant with pseudohypoaldosteronism found to have a deletion of 4q31.21q31.23, including
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A Rare Case of Mosaic Unbalanced Non-Robertsonian Translocation Involving Chromosomes 15 and 22 with Congenital Abnormalities in Monozygotic Twins. Mol. Syndromol. (IF 1.198) Pub Date : 2019-12-21 Emine I Atli,Engin Atli,Sinem Yalcintepe,Hakan Gurkan
Balanced de novo non-robertsonian translocations (non-RTs), which involve acrocentric chromosomes, are rare findings in clinical cytogenetics and may be associated with an abnormal phenotype. These translocations, detected by conventional karyotyping, are found in approximately 1:1,000 neonates. In most of these cases, one of the parents carries the same translocation. In this study, we report a rare
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Genes Positively Selected in Domesticated Mammals Are Significantly Dysregulated in the Blood of Individuals with Autism Spectrum Disorders. Mol. Syndromol. (IF 1.198) Pub Date : 2019-12-21 Antonio Benítez-Burraco
Human self-domestication (i.e., the presence of traits in our species that are commonly found in domesticated animals) has been hypothesized to have contributed to the emergence of many human-specific features, including aspects of our cognition and behavior. Signs of self-domestication have been claimed to be attenuated in individuals with autism spectrum disorders (ASD), this conceivably accounting
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Novel Ocular and Inner Ear Anomalies in a Patient with Myhre Syndrome. Mol. Syndromol. (IF 1.198) Pub Date : 2019-12-20 Semra Gürsoy,Filiz Hazan,Tülay Öztürk,Halil Ateş
Myhre syndrome is a rare autosomal dominant multisystemic disorder. Typical features of this disorder include distinctive facial appearance, deafness, intellectual disability, cardiovascular abnormalities, short stature, brachydactyly, and skeletal anomalies. Gain-of-function mutations in the SMAD4 gene are responsible for this syndrome. Herein, we present a 9.6-year-old Turkish girl with molecularly
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NUP188 Biallelic Loss of Function May Underlie a New Syndrome: Nucleoporin 188 Insufficiency Syndrome? Mol. Syndromol. (IF 1.198) Pub Date : 2019-12-10 Anna Sandestig,Karolina Engström,Alexander Pepler,Ingela Danielsson,Per Odelberg-Johnsson,Saskia Biskup,Anja Holz,Margarita Stefanova
There is no clearly established association between the gene NUP188 and human pathology. Only a few reports of patients with different clinical presentation and different heterozygous or compound heterozygous missense or splice region variants have been identified in several sequencing projects; however, a causative association between the clinical features and the identified variants has not been
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Cardiofaciocutaneous Syndrome Phenotype in a Case with de novo KRAS Pathogenic Variant. Mol. Syndromol. (IF 1.198) Pub Date : 2019-11-26 Aslihan Sanri,Hakan Gurkan,Selma Demir
Cardiofaciocutaneous (CFC) syndrome is one of the developmental disorders caused by a dysregulation of the Ras/mitogen-activated protein kinase (MAPK) pathway. RASopathies share overlapping clinical features, making the diagnosis challenging, especially in the newborn period. The majority of CFC syndrome cases arise by a mutation in the BRAF, MAP2K1, MAP2K2, or (rarely) KRAS genes. Germline KRAS mutations
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Previously Unreported COL7A1 Mutation in a Somali Patient with Dystrophic Epidermolysis Bullosa. Mol. Syndromol. (IF 1.198) Pub Date : 2019-11-16 Valeria Venti,Bruna Scalia,Alessandra Sauna,Maria Rita Nasca,Pierluigi Smilari,Andrea D Praticò,Agata Fiumara,Xena G Pappalardo,Piero Pavone
Epidermolysis bullosa (EB) encompasses a group of inheritable skin disorders characterized by various degrees of epithelial fragility that lead to cutaneous and mucosal blistering following negligible mechanical traumas. These disorders are clinically and genetically heterogeneous, ranging from mild skin involvement to severe disabling conditions with associated manifestations affecting the gastrointestinal
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Deep Phenotyping of Development, Communication and Behaviour in Phelan-McDermid Syndrome. Mol. Syndromol. (IF 1.198) Pub Date : 2019-11-05 Gilles Droogmans,Ann Swillen,Griet Van Buggenhout
Phelan-McDermid syndrome (PMS; also referred to as 22q13.3 deletion syndrome) is a congenital condition due to a microdeletion in the SHANK3 gene. Cognitive and communicative deficits as well as behaviour in the autism spectrum are often noticed in affected individuals. The aim of the present study was to obtain a detailed phenotype of the development, communication, and behaviour of 15 individuals
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Novel MECP2 Mutation c.1162_1172del; p.Pro388* in Two Patients with Symptoms of Atypical Rett Syndrome. Mol. Syndromol. (IF 1.198) Pub Date : 2019-07-02 Ulrike Bernstein,Stephanie Demuth,Oliver Puk,Birgit Eichhorn,Solveig Schulz
We report 2 cases of girls with MECP2 gene variants who do not have typical clinical features of Rett syndrome except for intellectual disability and seizures. Both patients present with adipositas, macrocephalia, precocious puberty, and seizures. They have prominent eyebrows and a short neck as well as short and plump fingers. Sequencing by NGS revealed a novel variant c.1162_1172del; p.Pro388* in
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Report of a Second Lebanese Family with Basel-Vanagaite-Smirin-Yosef Syndrome: Possible Founder Mutation. Mol. Syndromol. (IF 1.198) Pub Date : 2019-06-28 Pratibha Nair,Sandra Sabbagh,Sami Bizzari,Florian Brunner,Samantha Stora,Mahmoud T Al-Ali,Martin Gencik,Stephany El-Hayek,André Mégarbané
Basel-Vanagaite-Smirin-Yosef syndrome (OMIM 616449) is a rare autosomal recessive genetic disorder characterized by severe developmental delay and variable craniofacial, neurological, cardiac, and ocular anomalies in the presence of variants in the MED25 gene. So far, only a handful of patients have been reported with this condition globally. Here, we report an additional Lebanese family with 2 affected
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Concurrent Structural and Single Nucleotide Variation Resulting from a Single Replication-Based Mechanism. Mol. Syndromol. (IF 1.198) Pub Date : 2019-06-28 Martin Poot
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Defining the Critical Region for Intellectual Disability and Brain Malformations in 6q27 Microdeletions. Mol. Syndromol. (IF 1.198) Pub Date : 2019-06-21 Marcela D Hanna,Patricia N Moretti,Claudiner P de Oliveira,Maria T A Rosa,Beatriz R Versiani,Silviene F de Oliveira,Aline Pic-Taylor,Juliana F Mazzeu
Terminal microdeletions of the long arm of chromosome 6 are associated with a phenotype that includes multiple brain malformations, intellectual disability, and epilepsy. A 1.7-Mb region has been proposed to contain a gene responsible for the brain anomalies. Here, we present the case of a 12-year-old girl with multiple brain alterations and moderate intellectual disability with a 18-kb deletion in
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Co-Occurrence of Leber Congenital Amaurosis and Meckel Syndrome Type 1 in a Fetus: Is There a Lesson to Be Learned? Mol. Syndromol. (IF 1.198) Pub Date : 2019-06-14 Karthik Tallapaka,Shagun Aggarwal,Amrita Bhattacherjee,Aneek Das Bhowmik,Ashwin Dalal
A patient referred for prenatal diagnostics, after first-trimester ultrasound due to a previous child with Leber congenital amaurosis, was suggestive of a Meckel syndrome-like phenotype. Fetal autopsy confirmed the multiple anomalies, and whole-exome sequencing of the fetal DNA identified a pathogenic variant in the RPGRIP1 gene, previously identified in the elder sibling, and a variant causative of
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Further Delineation of the Microcephaly-Micromelia Syndrome Associated with Loss-of-Function Variants in DONSON. Mol. Syndromol. (IF 1.198) Pub Date : 2019-06-14 Hanadi A Abdelrahman,Anne John,Bassam R Ali,Lihadh Al-Gazali
The DONSON gene encodes the downstream neighbor of SON, a replisome component that stabilizes the replication fork during replication. A severe form of microcephalic dwarfism, microcephaly-micromelia syndrome (MIMIS), has been recently associated with DONSON biallelic loss of function. Affected fetuses suffer severe growth restriction, microcephaly, and variable limb malformations which result in intrauterine
更新日期:2019-11-01