Categoría: Open access
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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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Rapid minigene workflow for functional reclassification of splicing variants in hereditary cancer diagnostics
Background Next-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 …
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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
WHAT IS ALREADY KNOWN ON THIS TOPICRare disease genomic testing will occasionally reveal a highly actionable genetic variant unrelated to the reason for testing but of relevance to the patient or their family members. Guidance for managing such incid…
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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
Background Pontocerebellar 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 l…
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Unified genetic risk score for prostate cancer enables improved risk stratification for clinical decision-making
Background Current clinical approaches to inherited prostate cancer (PCa) risk rely on binary classification of pathogenic variant (PV) carrier status without accounting for gene-specific heterogeneity or polygenic risk. We developed an integrated gen…
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Unified genetic risk score for prostate cancer enables improved risk stratification for clinical decision-making
BackgroundCurrent clinical approaches to inherited prostate cancer (PCa) risk rely on binary classification of pathogenic variant (PV) carrier status without accounting for gene-specific heterogeneity or polygenic risk. We developed an integrated genet…
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Potential advantage of clinical exome sequencing in BRCA1/2-negative families: a retrospective study of a cohort of 500 patients at a high-risk for hereditary cancers
Background Hereditary cancer syndromes (HCSs) account for approximately 5–10% of all cancers and are frequently associated with pathogenic variants (PVs) in genes such as BRCA1 and BRCA2. Nevertheless, a substantial proportion of individuals wit…