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 […]
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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 […]
UKCGG Consensus Group guidelines for the management of patients with constitutional TP53 pathogenic variants
The TP53 gene is known as the “guardian of the cell” due to its crucial role in preventing cancer cells developing. Individuals with a pathogenic variant (spelling change ) in the TP53 gene are at a very high lifetime risk of developing cancer throughout childhood and adulthood, most commonly cancers of the bone and soft […]
Haploinsufficiency of the NF1 gene is associated with protection against diabetes
Neurofibromatosis type 1 (NF1) is a hereditary syndrome caused by mutations in a single gene, NF1. Kallionpää et al. used data from population-based cohort of Finnish patients with NF1 and nationwide health care registers, to study the association of NF1 and diabetes. They observed a reduced risk of diabetes, especially type 2 diabetes, among individuals […]