Categoría: Open access
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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…
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Congenital anaemia associated with loss-of-function variants in DNA polymerase epsilon 1
DNA polymerase epsilon (Pol ), a component of the core replisome, is involved in DNA replication. Although genetic defects of Pol have been reported to cause immunodeficiency syndromes, its role in haematopoiesis remains unknown. Here, we identified c…
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Genetic complexity of diagnostically unresolved Ehlers-Danlos syndrome
BackgroundThe Ehlers-Danlos syndromes (EDS) are heritable disorders of connective tissue (HDCT), reclassified in the 2017 nosology into 13 subtypes. The genetic basis for hypermobile Ehlers-Danlos syndrome (hEDS) remains unknown.MethodsWhole exome sequ…
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Neurofibromatosis type 1 mosaicism in patients with constitutional mismatch repair deficiency
Differential diagnosis between constitutional mismatch repair deficiency (CMMRD) and neurofibromatosis type 1 (NF1) is crucial as treatment and surveillance differ. We report the case of a girl with a clinical diagnosis of sporadic NF1 who developed a…
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Diagnostic genome sequencing improves diagnostic yield: a prospective single-centre study in 1000 patients with inherited eye diseases
Purpose Genome sequencing (GS) is expected to reduce the diagnostic gap in rare disease genetics. We aimed to evaluate a scalable framework for genome-based analyses ‘beyond the exome’ in regular care of patients with inherited retinal deg…
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Updates on diagnostic criteria for hereditary haemorrhagic telangiectasia in the light of whole genome sequencing of ‘gene-negative individuals recruited to the 100 000 Genomes Project
Hereditary haemorrhagic telangiectasia (HHT) is diagnosed clinically by the Curacao Criteria of spontaneous recurrent nosebleeds, mucocutaneous telangiectasia at characteristic sites, visceral involvement (arteriovenous malformations (AVMs); gastroint…
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Integrating a Polygenic Risk Score into a clinical setting would impact risk predictions in familial breast cancer
Background Low-impact genetic variants identified in population-based genetic studies are not routinely measured as part of clinical genetic testing in familial breast cancer (BC). We studied the consequences of integrating an established Polygenic Ri…