Categoría: Open access
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Obstetric history of women with m.3243A>G: an observational cohort study
BackgroundMitochondrial 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. Mi…
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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
BackgroundFamilial 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 genetica…
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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 guide…
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Further evidence of RNU4ATAC variants causing Joubert syndrome with skeletal involvement
RNU4ATAC is a non-coding gene involved in the minor spliceosome, and is mutated in a spectrum of syndromic skeletal disorders with recessive inheritance. Recently, biallelic RNU4ATAC pathogenic variants were detected in five patients presenting a co…
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Long-term efficacy of migalastat in females with Fabry disease
Background Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to GLA variants. Females with Fabry disease often experience diagnostic delays and an underappreciated disease burd…
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Refined genotype-phenotype correlations in neurofibromatosis type 1 patients with NF1 point variants
Background Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders. NF1 is caused by dominant loss-of-function pathogenic variants (PVs) of the tumour-suppressor gene NF1, which encodes neurofibromin, a negative regulator of rat s…
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APC I1307K and clinical management: insights from UK Biobank association analysis of colorectal and other cancer risks in Ashkenazi and non-Ashkenazi whites
Background APC c.3920T>A; p.Ile1307Lys (I1307K), prevalent in individuals of Ashkenazi Jewish (AJ) origin, has been associated with a modestly increased colorectal cancer (CRC) risk. Clinical recommendations for I1307K heterozygotes vary across c…
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Reproductive carrier screening for genetic disorders: position statement of the Canadian College of Medical Geneticists
Purpose and scope The aim of this position statement is to provide recommendations aimed at Canadian reproductive care clinicians and genetics professionals regarding the use of reproductive carrier screening for autosomal recessive and X-linked reces…
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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…
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PURA protein mislocalisation in the nucleus: mechanistic basis for transcriptional dysregulation and DNA unwinding deficits in a model of the p.L148Wfs*77 PURA variant
Background Heterozygous PURA (Purine-rich element-binding protein A) variants cause PURA syndrome, a neurodevelopmental disorder characterised by hypotonia, seizures and intellectual disability. Previous studies have focused on the effect of the PURA …