Etiqueta: #JMedGenet
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Novel in-frame variant in DES (p.Glu353dup) causes myofibrillar myopathy: clinical, in silico and functional studies
Background Desmin (DES) is a major intermediate filament protein involved in the structural integrity and function of striated muscles. Pathogenic mutations in DES are predominantly missense variants, causing isolated cardiomyopathy and combinations o…
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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 im…
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Refining the phenotypic spectrum of PNKP-related microcephaly: a study of 27 new patients
Background Biallelic pathogenic variants in PNKP are associated with microcephaly and early-onset seizures (MCSZ), ataxia with oculomotor apraxia type 4 and Charcot-Marie-Tooth disease type 2B2. Methods We describe the clinical and neuroimaging featu…
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Catatonia and regression in an autism spectrum disorder patient harbouring a BRSK2 frameshift mutation
Deleterious variants in the BRSK2 gene, which encodes a serine/threonine kinase crucial for neuronal polarisation and brain development, have recently been linked to the pathogenesis of autism spectrum disorder (ASD). However, comprehensive clinical d…
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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 …