Desmin (DES) is a key protein that helps muscle cells maintain their structure and function. In this study, we identified and characterized a previously unknown mutation in DES in an Argentine family affected by a muscle disease. Unlike most known DES mutations, this alteration is a small insertion whose disease-causing role was unclear. By combining […]
Latest articles
Refining the phenotypic spectrum of PNKP-related microcephaly: a study of 27 new patients
Primary microcephaly are genetic conditions that are characterized by small head circumference at birth and always associated with intellectual disability. However, early-onset seizures are prevalent in PNKP-related microcephaly. In this study, we present the clinical and molecular genetics findings of 27 patients carrying biallelic PNKP variants. Our findings showed that hypoplastic frontal lobe when associated […]
Obstetric history of women with m.3243A>G: an observational cohort study
Mitochondrial disease is a common type of inherited metabolic disease, typically caused by pathogenic variants in the maternally inherited mitochondrial DNA (mtDNA). In this study, we investigated a cohort of Finnish women harbouring the mtDNA variant m.3243A>G, the most common cause of adult mitochondrial disease. We found that these individuals may have an elevated risk […]
Haplotype studies and the use of a nearby tagging variant confirm a founder origin for an intragenic CYP11B1 inversion
Genomic inversions occur when a stretch of DNA flips over, reversing its orientation. The absence of copy-number change can make these variants hard to spot. In this commentary, Pagnamenta and colleagues examine an inversion recently reported by Janot et al. in a gene linked to disorders of sexual development. They show it can be detected […]
Analysis of familial exudative vitreoretinopathy (FEVR) cases in the UK 100 000 genomes project increases diagnostic rate and implicates heterozygous CTNND1 mutations in FEVR
Familial exudative vitreoretinopathy (FEVR) is a blinding disorder caused by abnormal development of retinal blood vessels. This study reanalyses whole genome sequence data from 59 individuals with FEVR in the UK 100,000 Genomes Project (100KGP). Bespoke analysis led to molecular diagnoses in 39%, almost doubling the diagnostic success of standard analyses. New cases solved include […]
Sequencing every UK newborn: why cold storage economics should shape policy
Sequencing every UK baby’s genome is often presented as a simple route to personalised medicine. My article argues that the real challenge is not the science but what happens to the vast files afterwards. If the NHS keeps every genome in expensive “always on” cloud storage, the ten-year bill could run to hundreds of millions […]
Intragenic loss-of-function variants in transcription factors MAZ, FOXP1, and SIN3B in colobomatous microphthalmia
Ocular coloboma is a rare developmental eye disorder that can result in childhood blindness. Despite numerous genes being associated with coloboma, many cases are unexplained, suggesting novel genes remain to be discovered. One approach to gene identification is reviewing variants in genes located within known chromosomal deletions associated with structural eye defects. We thus identified […]
ACTH-secreting atypical carcinoid lung tumour expanding the Lynch syndrome spectrum
Lynch syndrome is a genetic condition associated with tumours of the colon, reproductive organs, and urinary tract. Less commonly, neuro-endocrine tumours have also been reported. We describe the first case of a Lynch syndrome patient presenting with a neuroendocrine lung tumour manifesting as cortisol excess (Cushing’s syndrome) in a middle-aged woman. In addition to the […]
Expert endoscopic surveillance in CDH1 pathogenic variant carriers seems safe, even after positive (pT1a) biopsies
In this retrospective study, Patrick Benusiglio and colleagues show that expert surveillance is safe in the hereditary diffuse gastric cancer syndrome. Among 20 CDH1 pathogenic variant carriers undergoing annual upper gastrointestinal endoscopy, none has developed aggressive signet ring cell carcinoma of the stomach, regardless of the presence of intramucosal (pT1a) cancer foci on biopsies. This […]
Advancing genotype-phenotype analysis through 3D facial morphometry: insights from Cri-du-Chat syndrome
Cri-du-Chat Syndrome (CdCS) is a rare genetic disorder caused by missing pieces (deletions) of chromosome 5. This study compared 3D facial photos of 29 individuals with CdCS and thousands of unaffected individuals to understand how different deletions affect facial features. Large deletions caused consistent features like a short space between the nose and upper lip, […]