Categoría: Open access
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Genotype-phenotype associations in Alström syndrome: a systematic review and meta-analysis
Background Alström syndrome (ALMS; #203800) is an ultrarare monogenic recessive disease. This syndrome is associated with variants in the ALMS1 gene, which encodes a centrosome-associated protein involved in the regulation of several ciliary a…
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Recessive MECR pathogenic variants cause an LHON-like optic neuropathy
Background Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder characterised by complex I defect leading to sudden degeneration of retinal ganglion cells. Although typically associated with pathogenic variants in mitochondrial…
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Prevalence and clinical implications of germline pathogenic variants in cancer predisposing genes in young patients across sarcoma subtypes
Background Sarcomas are a rare and diverse group of cancers occurring mainly in young individuals for which an underlying germline genetic cause remains unclear in most cases. Methods Germline DNA from 177 children, adolescents and young adults with …
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Reduced penetrance of gene variants causing amyotrophic lateral sclerosis
BackgroundAmyotrophic lateral sclerosis overlaps aetiologically and genetically with frontotemporal dementia and occurs in both familial and apparently sporadic forms. The most commonly implicated genes are C9orf72, SOD1, TARDBP and FUS. Penetrance of …
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Risk-reducing decisions regarding germline BRCA pathogenic variant: focusing on the timing of genetic testing and RRSO
BackgroundIn Japan, the public insurance policy was revised in 2020 to cover hereditary breast and ovarian cancer (HBOC), including genetic testing and surveillance, for patients with breast cancer (BC). Consequently, the demand for risk-reducing salpi…
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Co-design of patient information leaflets for germline predisposition to cancer: recommendations for clinical practice from the UK Cancer Genetics Group (UKCGG), Cancer Research UK (CRUK) funded CanGene-CanVar Programme and the Association of Genetic Nurse Counsellors (AGNC)
Background Testing for germline pathogenic variants (GPVs) in cancer predisposition genes is increasingly offered as part of routine care for patients with cancer. This is often urgent in oncology clinics due to potential implications on treatment and…
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Short-read whole genome sequencing identifies causative variants in most individuals with previously unexplained aniridia
BackgroundClassic aniridia is a highly penetrant autosomal dominant disorder characterised by congenital absence of the iris, foveal hypoplasia, optic disc anomalies and progressive opacification of the cornea. >90% of cases of classic aniridia are …
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Ancestry, race and ethnicity: the role and relevance of language in clinical genetics practice
BackgroundThe terms ancestry, race and ethnicity are used variably within the medical literature and within society and clinical care. Biological lineage can provide an important context for the interpretation of genomic data, but the language used, an…
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Heterozygous COL17A1 variants are a frequent cause of amelogenesis imperfecta
BackgroundCollagen XVII is most typically associated with human disease when biallelic COL17A1 variants (>230) cause junctional epidermolysis bullosa (JEB), a rare, genetically heterogeneous, mucocutaneous blistering disease with amelogenesis imperf…
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Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study
BackgroundPegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated gl…