Etiqueta: #JMedGenet
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Obstetric history of women with m.3243A>G: an observational cohort study
Background Mitochondrial diseases are genetic disorders arising from pathogenic variants in nuclear or mitochondrial DNA (mtDNA) characterised by respiratory chain dysfunction. Clinical manifestations are diverse, and treatment is mostly symptomatic. …
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Haplotype studies and the use of a nearby tagging variant confirm a founder origin for an intragenic CYP11B1 inversion
We read with interest the report by Janot et al describing an individual with elevated steroid precursors suggestive of 11β-hydroxylase deficiency and clinical features consistent with congenital adrenal hyperplasia (CAH).1 A single paternally in…
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Analysis of familial exudative vitreoretinopathy (FEVR) cases in the UK 100 000 genomes project increases diagnostic rate and implicates heterozygous CTNND1 mutations in FEVR
Background Familial exudative vitreoretinopathy (FEVR) is an inherited eye disease characterised by the incomplete development of the retinal vasculature. Over 10 genes have been associated with FEVR, but there are still a substantial number of geneti…
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Evidence for pathogenicity of BRCA2 c.8351G>A p.(Arg2784Gln) and the challenges in classification of pathogenic variants with reduced penetrance
Background The BRCA2 c.8351G>A p.(Arg2784Gln) variant has long been classified as a variant of uncertain significance (VUS) due to conflicting evidence used in variant classification. This study aims to clarify its pathogenicity and associated risk…
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Sequencing every UK newborn: why cold storage economics should shape policy
Whole-genome sequencing (WGS) for every UK newborn is hailed as a leap towards lifelong personalised medicine, yet policymakers have scarcely examined the informatics iceberg beneath the initiative: where, and at what cost, will millions of genomes be…
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Challenges associated with disclosing results from whole genome sequencing to diagnose paediatric rare diseases: analysis of parent-clinician interactions
Background Whole genome sequencing (WGS) has recently been introduced as a diagnostic test for patients with particular rare diseases in the National Health Service (NHS) in England. Little is known about the process of communicating results from WGS …
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Intragenic loss-of-function variants in transcription factors MAZ, FOXP1 and SIN3B in colobomatous microphthalmia
Despite the identification of many genes involved in developmental eye phenotypes, a large percentage of families lack genetic diagnoses, suggesting novel mechanisms remain to be discovered. Large deletions of 16p11.2, 3p14 or 19p13.11 regions involvi…
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Association for Clinical Genomic Science (ACGS) guidelines for the classification of oncogenicity of somatic variants in cancer: recommendations by the UK somatic variant interpretation group (SVIG-UK)
Comprehensive genomic testing in routine cancer care pathways has created the need to interpret the consequences of somatic (acquired) genomic variants beyond the currently well-characterised driver variants in cancer gene hotspots. While several guid…
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ACTH-secreting atypical carcinoid lung tumour expanding the Lynch syndrome spectrum
Neuroendocrine tumours (NETs) are increasingly associated with Lynch syndrome (LS). In this autosomal dominant cancer predisposition syndrome, a somatic mutation in addition to a germline pathogenic variant is required for tumour development. We descr…
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Development of a functional assay for the characterisation of SMAD4 variants from the French haemorrhagic hereditary telangiectasia cohort
Background Hereditary haemorrhagic telangiectasia (HHT) and juvenile polyposis syndrome (JPS) can be caused by SMAD4 pathogenic variants. SMAD4 is a common transcription factor of the BMP/TGFβ signalling pathway. In this study, we developed a cel…