Limb-girdle muscular dystrophies (LGMD) are muscle disorders with a genetic cause. TRAPCC11 is one of the many genes involved in LGMD, which leads to muscle weakness from early childhood, intellectual disability and elevated muscle enzymes in blood test, among other symptoms. In this study, we report 25 Roma individuals who share the same homozygous variant […]
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Mutations in VWA8 cause autosomal-dominant retinitis pigmentosa via aberrant mitophagy activation
Retinitis pigmentosa (RP) is the most common hereditary retinal dystrophy. This study identified variant c.3070G>A;c.4558C>T (p.Gly1024Arg; p.Arg1520Ter) in VWA8 which is linked to retinal diseases from a four generation Chinese family with autosomal dominant retinitis pigmentosa. Then this study showed that the VWA8 variant can induce mitochondrial defects, resulting in the activation of mitophagy and […]
TBX20 loss-of-function variants in families with left ventricular non-compaction cardiomyopathy
TBX20 gene encodes a transcription factor that is essential for heart development. Recent experimental data implicate loss of TBX20 function in the development of left ventricular noncompaction cardiomyopathy (LVNC) but supporting clinical and genetic data in affected families is scarce. We report a series of four families with TBX20 loss-of-function variants that segregate with LVNC. […]
Opportunistic genetic screening increases the diagnostic yield and is medically valuable for care of patients and their relatives with hereditary cancer
Patients with suspicion of hereditary cancer are referred to cancer genetic counselling units, where they are assessed for genetic testing suitability. If so, those genes known to be associated with specific cancer or syndrome predisposition are analysed by a state-of-the-art technology known as next-generation sequencing (NGS). Additionally, NGS enables the analysis of a broad range […]
Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature
KBG syndrome is a rare neurodevelopmental disorder caused by heterozygous variants in the ANKRD11 gene and is one of the most prevalent genetic syndromes. Many reports over the years have delineated the variable phenotypic spectrum of this condition but the skeletal and in particular the neuroimaging features remain poorly defined. We have systematically analyzed the […]
Genetic and phenotypic spectrum of non-21-hydroxylase-deficiency primary adrenal insufficiency in childhood: data from 111 Chinese patients
Primary adrenal insufficiency (PAI) is a rare but life-threatening condition. We retrospectively analyzed the genetic and clinical characteristics of 111 non-21OHD PAI patients in China. STAR and NR0B1 were the most frequently mutated genes in Chinese patients with non-21OHD PAI. The age of onset was dependent on etiology. Clinical characteristics (17OHP, VLCFA, external genitalia, blood […]
Clinical, genetic and biochemical signatures of RBP4-related ocular malformations
Vitamin A plays a crucial role in both eye development during pregnancy and function in adulthood. Mutations in the gene encoding its blood transporter, named RBP4, have been associated with two rare conditions: recessive degeneration of retina and dominant malformations of ocular globe. We report here 7 new families (13 individuals) with eye malformations caused […]
Use of genome sequencing to hunt for cryptic second-hit variants: analysis of 31 cases recruited to the 100 000 Genomes Project
In some inherited conditions, both copies of a gene must be altered (“variant”) to cause symptoms; these are known as autosomal recessive disorders. Some patients with suspected autosomal recessive disorders were recruited for whole genome sequencing (WGS) through the 100,000 Genomes Project after only one causative variant was detected. Clinical testing may not detect some […]
Germline HPF1 retrogene insertion in RB1 gene involved in cancer predisposition
About half of the human genome is composed of repeated sequences derived from mobile elements, generally without pathogenic effect. These include retrogenes, which derive from mRNAs retrotransposed into the genome and may encode functional proteins. Transposition of mobile elements are important elements involved in the evolution of species. Germline pathogenic variants in RB1 gene confer […]
CHEK2 is not a Li-Fraumeni syndrome gene: time to update public resources
CHEK2 is a moderate risk cancer predisposition gene, but is currently listed as “Li-Fraumeni syndrome 2” in public resources used by medical geneticists and patients. Li-Fraumeni syndrome experts consider that TP53 is the only gene causing this multi-cancer syndrome. Our comprehensive comparison of phenotypic characteristics of CHEK2 and TP53 carriers undergoing multigene panel testing provides conclusive evidence that none of the phenotypes significantly associated with TP53, including extremely early onset […]