Hearing loss (HL) is one of the most prevalent disabilities worldwide and is highly heritable. Nevertheless, genetics of adult-onset HL is poorly understood. In this study, a DNA-variant was identified in the RIPOR2 gene as a frequent cause of HL. The HL associated with the RIPOR2-variant is highly variable and the age of onset, on […]
Latest articles
A novel form of rhizomelic skeletal dysplasia associated with a homozygous variant in GNPNAT1
Skeletal dysplasias are disorders which involve bone deformities and short stature. The genetic causes for some of these disorders are unknown. We describe for the first time a missense variant of a gene, GNPNAT1 which results in severe short stature in four patients due to extreme shortening of the proximal segments of the limbs. GNPNAT1 […]
Heritable genetic variants in key cancer genes link cancer risk with anthropometric traits
Physical measures, like height and weight, are known to associate with cancer risk. However, the reasons for these associations are not well understood. Here we explore if differences in our genetic code might contribute to these associations. We study the genomes of 500,000 people living in the United Kingdom and show that differences in the genetic code […]
Exome and genome sequencing in adults with undiagnosed disease: a prospective cohort study
Genetic diseases affect up to 1/50 adults, causing significant complications in many cases. Standard genetic tests often miss the diagnosis, leaving these adults without treatment options and their families without specific risk information. In our study, we used exome and genome sequencing in 47 families who were suspected to have a genetic disease, but remain undiagnosed […]
Loss of imprinting of the human-specific imprinted gene ZNF597 causes prenatal growth retardation and dysmorphic features: implications for phenotypic overlap with Silver-Russell syndrome
Various kinds of genetic and epigenetic changes can cause growth failure before and after birth. Through screening of a cohort of babies born small for gestational age, we have encountered a 6-year-old boy with prenatal growth restriction and some specific physical features. Detailed molecular analyses have revealed epigenetic alteration (epimutation) of the ZNF597 gene on […]
Sporadic vestibular schwannoma: a molecular testing summary
Our study reviews the prevalence of undiagnosed tumour predisposition disorders, schwannomatosis and NF2, in apparent cases of sporadic vestibular schwannoma (VS). We found that undiagnosed predisposition to these tumours may account for a significant proportion of apparently sporadic VS cases, especially in those presenting at a lower age. Somatic mutations in NF2 were common throughout […]
Co-occurrence of germline BRCA1 and CDH1 pathogenic variants
We report the case of a 91-year-old woman diagnosed with breast cancer at the age of 52. She had a family history of breast and gastric cancers. A genetic predisposition to cancer was suspected. Surprisingly, we found not one but two genetic predispositions to cancer in the family, with alterations in both BRCA1 and CDH1 […]
A novel loss-of-function mutation in HERC2 is associated with severe developmental delay and paediatric lethality
Our study outlines the discovery of a novel null mutation in the HERC2 gene, which is a significant advance in delineating the broad range of neurodevelopmental conditions that are caused by mutations in this gene. We describe a family with children affected with a very severe developmental disorder, causing paediatric lethality in two individuals. The […]
Wide range of reduced penetrance alleles in spinal and bulbar muscular atrophy: a model-based approach
Spinal and bulbar muscular atrophy (Kennedy’s disease) is an X-linked motor neuron disorder caused by a CAG repeat expansion in the androgen receptor gene. Traditionally, alleles with 38 or more CAG repeats are considered fully penetrant in male carriers. By comparing, through systematic review and meta-analysis, the distribution of CAG repeat sizes between 2,576 patient […]
Clinical spectrum and genetic variations of LMNA-related muscular dystrophies in a large cohort of Chinese patients
LMNA-related muscular dystrophies are a group of rare muscle diseases caused by detrimental changes (i.e. mutations) in the LMNA gene. They exhibit a wide spectrum of clinical symptoms. We reported our clinical and genetic findings from 84 patients recruited from many neuromuscular centers in China over 12 years. We found many new mutations of the […]