TMEM16A deficiency: a potentially fatal neonatal disease resulting from impaired chloride currents

In a consanguineous family, we identified a truncating pathogenic variant in TMEM16A. As a result, the patients develop a severe neonatal disorder mimicking necrotizing enterocolitis. Electrophysiological studies demonstrate absence of TMEM16A-mediated chloride currents and severe impairment of CFTR, the ion channel mutated in Cystic Fibrosis. Despite this, the patients had no respiratory symptoms but instead […]

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Description of a multidisciplinary model of care in a French cohort of adult patients with tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Due to the various manifestations of TSC and their potential complications, a multidisciplinary care approach is recommended. This study provides a precise description of a French cohort of 90 patients suffering from STB in adulthood. Their quality of life, i.e. physical health and mental […]

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Ethnic-specific BRCA1/2 variation within Asia population: evidence from over 78 000 cancer and 40 000 non-cancer cases of Indian, Chinese, Korean and Japanese populations

BRCA mutation is genetic predisposition for breast and ovarian cancer. BRCA mutation is well determined as ethnic-specific by studies in Ashkenazi Jewish, Polish and Icelandic populations. However, sufficient evidence is lack to determine if ethnic-specific BRCA mutation is also present in the largest and the most diversified Asia population. We performed a comprehensive data mining to […]

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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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