Categoría: Open access
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Solid tumours in RASopathies: insights from a large monocentric cohort and systematic review of the literature
BackgroundDysregulation of the RAS-mitogen-activated protein kinase signalling pathway underlies RASopathies, a family of neurodevelopmental disorders associated with variable cancer predisposition. However, the prevalence and spectrum of solid tumours…
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Hypertrophic cardiomyopathy: a genome-wide association meta-analysis and polygenic risk score
BackgroundHypertrophic cardiomyopathy (HCM) is a heritable trait with marked variability in expression and outcomes. Our aims were to discover new genetic loci associated with HCM and to test the effect of a new polygenic risk score (PRS) on incidence,…
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Exome sequencing and large-scale analysis of electronic medical record-linked biobank data identify candidate deafness genes
IntroductionRapid advances in whole-exome sequencing (WES) have enabled large-scale detection of pathogenic variants. Although hundreds of genes are implicated in hearing loss, up to half of inherited cases remain unsolved, limiting eligibility for gen…
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Exploring the clinical and mutational spectrum of MORC2-associated disorders
BackgroundPathogenic missense variants in the MORC2 gene are associated with two distinct disorders: Charcot-Marie-Tooth disease type 2Z (CMT2Z) and the recently described DIGFAN (developmental delay, impaired growth, dysmorphic facies and axonal neuro…
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Rapid minigene workflow for functional reclassification of splicing variants in hereditary cancer diagnostics
BackgroundNext-generation sequencing of cancer predisposition genes is routinely used in hereditary cancer diagnostics. However, a substantial fraction of detected variants remains clinically unresolved. Using a customised 77-gene panel, we analysed 21…
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Founder variant in OTOG causing non-syndromic sensorineural hearing loss in Irish traveller population
Deafness is a common multifactorial sensory disorder with numerous underlying causes (genetic, environmental) and a broad range of impact on humans. To date, 156 non-syndromic hearing loss-associated genes have been identified (DFN) and 75%–80% f…
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The British Society for Genetic Medicine guidance on managing incidental findings identified during rare disease genomic testing
BackgroundGenomic testing will occasionally identify a highly actionable genetic variant or other finding that is not related to the reason for testing. Such incidental findings may be relevant to the patient undergoing testing or to their family membe…
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The British Society for Genetic Medicine guidance on managing incidental findings identified during rare disease genomic testing
BackgroundGenomic testing will occasionally identify a highly actionable genetic variant or other finding that is not related to the reason for testing. Such incidental findings may be relevant to the patient undergoing testing or to their family membe…
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Single-cell transcriptomics identifies neural fate disruption and glial reprogramming caused by RARS2 deficiency
BackgroundPontocerebellar hypoplasia type 6 (PCH6) is caused by biallelic pathogenic variants in RARS2, encoding mitochondrial arginyl-tRNA synthetase. Although mitochondrial dysfunction is a recognised feature, how RARS2 deficiency disrupts neural lin…
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Single-cell transcriptomics identifies neural fate disruption and glial reprogramming caused by RARS2 deficiency
BackgroundPontocerebellar hypoplasia type 6 (PCH6) is caused by biallelic pathogenic variants in RARS2, encoding mitochondrial arginyl-tRNA synthetase. Although mitochondrial dysfunction is a recognised feature, how RARS2 deficiency disrupts neural lin…