Categoría: JMG First
-
Refining the phenotypic spectrum of PNKP-related microcephaly: a study of 27 new patients
BackgroundBiallelic 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.MethodsWe describe the clinical and neuroimaging features o…
-
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 de…
-
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…
-
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 inh…
-
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…
-
Evidence for pathogenicity of BRCA2 c.8351G>A p.(Arg2784Gln) and the challenges in classification of pathogenic variants with reduced penetrance
BackgroundThe 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 risks …
-
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 …
-
Challenges associated with disclosing results from whole genome sequencing to diagnose paediatric rare diseases: analysis of parent-clinician interactions
BackgroundWhole 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 to…
-
Intragenic loss-of-function variants in transcription factors MAZ, FOXP1 and SIN3B in colobomatous microphthalmia
Despite the identification of many genes involved in developmental eye phenotypes, a large percentage of families lack genetic diagnoses, suggesting novel mechanisms remain to be discovered. Large deletions of 16p11.2, 3p14 or 19p13.11 regions involvin…
-
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…