Biallelic variant in cyclin B3 is associated with failure of maternal meiosis II and recurrent digynic triploidy

Fetus triploidy is a common cause of early miscarriages. In some cases, genetic predisposition has been suspected, but the genes involved are unknown. Here we explored the genetic cause of recurrent pregnancy loss associated with fetus triploidy in an Iranian family. We found a mutation in the cyclin B3 gene that is normally required to […]

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De novo mutations of SCN1A are responsible for arthrogryposis broadening the SCN1A-related phenotypes

Arthrogryposis multiplex congenita (AMC) is characterized by congenital joint contractures due to reduced fetal movements and includes a large spectrum of diseases. We show for the first time that de novo SCN1A variants are responsible for AMC indicating a critical role of SCN1A in motor development. SCN1A encodes a component of sodium channels which underlie […]

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Systematic evaluation of olfaction in patients with hereditary cystic kidney diseases/renal ciliopathies

Cilia are antenna-like protrusions found on almost every human cell type that are involved in the transmission of various sensations including the sense of smell. Thus, genetic defects disrupting the functional or structural integrity of cilia may result in olfactory dysfunction. Renal ciliopathies are among the most abundant representatives of these genetic disorders. Here, we […]

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Delineation of a new fibrillino-2-pathy with evidence for a role of FBN2 in the pathogenesis of carpal tunnel syndrome

Although carpal tunnel syndrome (CTS) is the most common form of peripheral entrapment neuropathy, its pathogenesis remains largely unknown. We report here on a unique family in which CTS occurred in subsequent generations at an unusually young age. Additional clinical features included brachydactyly and short Achilles tendons. We identified a novel heterozygous variant (p.Phe1670Cys) in […]

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RASA1 phenotype overlaps with hereditary haemorrhagic telangiectasia: two case reports

Genetic disorders may overlap in terms of their clinical expression and all mutations are not yet totally disclosed. We report herein two cases of RASA 1 syndrome mimicking hereditary hemorrhagic telangiectasia (HHT). The two cases illustrate a phenotype presentation of CM-AVM1 overlapping with the classical description of HHT. Indeed, visceral involvement and nasal telangiectasias in […]

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A novel homozygous variant in TRAPPC2L results in a neurodevelopmental disorder and disrupts TRAPP complex function

We report three siblings with neurodevelopmental delays from an Ashkenazi Jewish family with a homozygous variant (p.Ala2Gly) in TRAPPC2L gene, identified by whole genome sequencing. We previously reported another TRAPPC2L variant (p.Asp37Tyr) in two individuals with neurodevelopmental delay plus additional clinical findings. TRAPPC2L encodes a subunit of the conserved TRAPP complexes that functions in transport of vesicles between organelles. Interestingly, functional […]

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Determinants of quality of life in Rett syndrome: new findings on associations with genotype

This study examined how the type of genetic mutation, function and health affect quality of life in Rett syndrome. Better walking and feeding skills and less frequent seizures were associated with better quality of life and poor sleep and behavioural difficulties with poorer quality of life. Compared to other mutations, individuals with the p.Arg294* mutation […]

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Biallelic variants in BRCA1 gene cause a recognisable phenotype within chromosomal instability syndromes reframed as BRCA1 deficiency

BRCA1 gene is associated with breast-ovarian cancer susceptibility, however, carrying two variants in this gene causes a condition recognized as a very rare form of Fanconi Anemia. Here we present clinical features of nine individuals carrying two variants in BRCA1 gene, in order to understand the patients’ health risk. Features include growth failure, small head […]

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Frameshift mutation of Timm8a1 gene in mouse leads to an abnormal mitochondrial structure in the brain, correlating with hearing and memory impairment

Deafness-Dystonia-Optic Neuronopathy (DDON) syndrome is a rare X-linked inherited disease characterized by progressive deafness, dystonia, ataxia, visual problems, and memory deficit, which is caused by mutations in the gene DDP1/TIMM8A. The encoded protein, Tim8a, is a mitochondrial protein. In the present study, we found a novel mutation in the DDP1 gene (NM_004085.3, c.82C>T, p.Q28X) and […]

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