Categoría: Open access
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Inherited variants in autosomal dominant disease genes are a significant cause of fetal structural anomalies
BackgroundMonogenic disorders are a major cause of fetal structural anomalies. Most genetic diagnoses involve de novo, biallelic or X linked variants; however, inherited variants in autosomal dominant disease genes have been detected across multiple st…
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Later age of natural menopause among women with the pathogenic CHEK2 c.1100delC variant: a validation study
BackgroundThe average age of natural menopause (ANM) for European women is 50–52 years. Reproductive risk and lifestyle factors have been found to be associated with ANM. Furthermore, a genome-wide association study found that women with a CHEK2 …
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Frequency of familial hypercholesterolaemia-causing genetic variants in the 100 000 Genomes Project cohort: whole genome sequencing analyses of 77 260 participants
BackgroundHeterozygous Familial Hypercholesterolaemia (HeFH) is caused by pathogenic variants in LDLR, APOB, APOE or PCSK9, leading to elevated low-density lipoprotein-cholesterol and increased cardiovascular risk. In the UK, HeFH affects ~1 in 288 ind…
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MITF (p.E318K) and renal cell carcinoma: current evidence does not support an effect
The microphthalmia-associated transcription factor (MITF) is a key regulator of melanocyte development, function and survival. The p.E318K variant affects SUMOylation at K316 and has been shown to alter MITF’s genome occupancy, potentially influe…
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How do clinician and parent-reported data differ? An analysis of similarity and difference in the datasets from a cross-syndrome genetics cohort study (GenROC)
BackgroundParent/patient-reported (PRD) datasets provide ready access to phenotypic data for monogenic neurodevelopmental disorders, yet their concordance with clinical data is unclear.MethodsIn the GenROC study, 547 children (mean age 7.6 years, balan…
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Targeting autophagy in Duchenne muscular dystrophy: mechanistic insights and emerging therapeutic strategies
Duchenne muscular dystrophy (DMD) is a severe X-linked myopathy characterised by progressive skeletal and cardiac muscle degeneration, loss of ambulation, respiratory failure and premature mortality. Although corticosteroids and gene therapies have imp…
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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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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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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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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…