Neurofibromatosis type 1 (NF1) is a genetic condition characterized by increased risk of developing tumors, as well as various other physical and neurological manifestations. NF1 women were previously reported to have an increased risk of breast cancer. There are different genetic variants causing NF1: in ~5-10% of patients, large deletions of the entire NF1 locus […]
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Recontact to return new or updated PALB2 genetic results in the clinical laboratory setting
Duty to re-contact patients for updated genetic test results is a widely discussed topic and is routinely practiced by clinical laboratories. However, publications documenting results from retrospective testing are lacking. Within a cohort of 2977 individuals with Hereditary Breast and Ovarian Cancer and previously negative or inconclusive BRCA1/BRCA2 results, reanalysis found a new pathogenic variant […]
Germline testing of BRCA1, BRCA2, PALB2 and CHEK2 c.1100delC in 1514 triple negative familial and isolated breast cancers from a single centre, with extended testing of ATM, RAD51C and RAD51D in over 400
Alterations of certain genes may place women at increased risk of developing a subtype of breast cancer not expressing hormone receptors, triple negative breast cancer (TNBC). We undertook a review of the gene alterations seen in women in Manchester with TNBC and showed there is an increased risk of developing TNBC where there is an […]
Reduced penetrance of gene variants causing amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are incurable neurodegenerative diseases with shared pathology and genetics . We know how common ALS and FTD are, how often they run in families and how often specific genes are implicated. We used published literature and population-level data about genomic variation to calculate how common disease-causing variants […]
Short-read whole genome sequencing identifies causative variants in most individuals with previously unexplained aniridia
Classical aniridia is an eye malformation caused by the loss of one working copy of the PAX6 gene, but a minority of cases remain genetically unsolved. We sequenced the whole genomes of 37 affected families (51 individuals) where PAX6 had previously been sequenced but no causative mutation was found. We found a genetic cause in 22 (60%) families. 19 cases had […]
Ancestry, race and ethnicity: the role and relevance of language in clinical genetics practice
Clinicians are often asked to document a patient’s ethnicity when requesting certain types of medical investigations. For example, the genomic medicine service in England wants this information to help guide the interpretation of certain genetic findings. In the US, a patient’s race might be similarly documented. However, the terms ethnicity, or race, or indeed ancestry, […]
Clinical and genetic spectrum of RNF216-related disorder: A new case and literature review
RNF216-related disorder is a rare neuroendocrine disease resulting from RNF216 gene mutations with diverse symptoms and inheritance pattern. This study reported a new case with a novel causative RNF216 variant and reviewed all individuals with causative RNF216 variants in previous reports. We found that ataxia was the most frequent initial symptoms in individuals under 30 […]
Heterozygous COL17A1 variants are a frequent cause of amelogenesis imperfecta
Mutations in the COL17A1 gene are known to cause the recessively inherited skin blistering disease junctional epidermolysis bullosa in some patients and a dominant corneal ulcerative disease in others. There are also hints in the literature of a link to tooth defects, but these have not been fully documented. Here we show that COL17A1 mutations […]
Update of the UMD-VHL database: classification of 164 challenging variants based on genotype–phenotype correlation among 605 entries
The von Hippel Lindau (VHL) disease is an a hereditary tumor syndrome that predisposes to retinal and central nervous system hemangioblastomas, pheochromocytomas, clear cell renal cell carcinoma, pancreatic neuroendocrine tumors and other tumors. The VHL disease is caused by germline VHL mutation that require accurate classification. The TENGEN and PREDIR networks has collected and interpreted the data […]
Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomized phase 3 BALANCE study
BALANCE is the first study directly comparing pegunigalsidase alfa with agalsidase beta for the treatment of patients with Fabry Disease (FD). At enrollment, participants had received previous agalsidase beta treatment for 6 years on average and had worsening kidney function. The participants were then randomly assigned to receive pegunigalsidase alfa or continue agalsidase beta. Results […]