We have previously estimated that one in two million people will develop bilateral vestibular schwannomas by chance. We show for the first time molecular proof that a man who developed bilateral vestibular schwannomas aged 52 and 67 years of age had developed these by independent events in the NF2 gene with no evidence of a […]
Category: Uncategorized
A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype (Contributed by Nancy Hamel)
The recent discovery of a new mutation in the DNA mismatch repair gene PMS2 that is recurrent in the Inuit population surrounding Hudson Bay, Canada offers new insights suggesting that even a small, residual function of the gene in patients is sufficient to delay the age of onset of tumours. This new finding adds to […]
BRCA1 Circos: a visualisation resource for functional analysis of missense variants (Contributed by Dr. Alvaro N. Monteiro)
Carriers of germline pathogenic variants in BRCA1 have a significantly increased risk of breast and ovarian cancers. However, genetic testing may also uncover a variant of unknown significance (VUS). Due to the rarity of these variants clinical and family data are usually lacking to determine cancer risk association. Functional assays can be used to assess […]
Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing
Learning outcomes After completing this module you should be able to: Be aware of the genetic heterogeneity of ID and the diagnostic yield of different approaches to investigation Understand the challenges associated with interpreting variants identified by next generation sequencing (NGS) and the principles behind assigning causality Understand the strengths and weaknesses of a targeted […]
DCAF4, a novel gene associated with leucocyte telomere length (Contributed by Dr. Massimo Mangino)
Leukocyte telomere length (LTL) is associated with a number of diseases. In particular, telomeres are short in patients with cardiovascular disease and long in patients with different types of cancer such as melanoma. In our study we identified a novel gene (DCAF4) associated with LTL in the general population. Our finding expands the spectrum of genes […]
MuSK – a novel gene for fetal death (Contributed by Dr. Maria Wilbe)
Fetal akinesia deformation sequence (FADS) is a broad spectrum of syndromes characterized by reduced or loss of fetal movement, arthrogryposis, intrauterine growth restriction and developmental abnormalities. In this study, we identified a novel gene, MuSK (muscle-specific receptor tyrosine kinase), by whole exome sequencing in a Swedish family trio with fetuses affected by FADS. MuSK is […]
Mutation in RNF113A that shines a new light on trichothiodystrophy (Contributed by Dr. Mark Corbett)
The trichothiodystrophies (TTD) are characterised by brittle, sulphur deficient hair that has an unusual tiger-tail banding pattern under polarising light microscopy. People affected by TTD can experience a range of symptoms including dry skin, short stature, intellectual disability and susceptibility to infection. About half of the patients have an inability to properly repair DNA damage […]
Evaluation of somatic mutations in tibial pseudarthrosis samples in neurofibromatosis type 1 (Contributed by Dr. David Stevenson)
Genetic changes of both NF1 genes are postulated to be necessary for the development of tibial pseudarthrosis in individuals with neurofibromatosis type 1 (NF1). However, the tissue origin of the “second hit” mutation remains unclear. Macro-sections of tibial pseudarthrosis tissue were exome sequenced, as well as a blood sample from a child with NF1. A […]
Mutations in COA3 cause isolated complex IV deficiency associated with neuropathy, exercise intolerance, obesity, and short stature (Contributed by Dr. Elsebet Ostergaard)
Defects in complex IV of the respiratory chain may result in a variety of phenotypes and be caused by mutations in 20 genes, most of which are involved in assembly of the complex. Here, we have for the first time identified mutations in COA3 as a cause of complex IV deficiency in a patient with […]
mirTrios: an integrated pipeline for detection of de novo and rare inherited mutations from trios-based next-generation sequencing (Contributed by Dr. Jinyu Wu)
The rapid advances of Next-generation sequencing (NGS) technologies have greatly facilitated clinical genetic diagnosis of sporadic disease genome-widely. However, the vast amount of mutations generated by NGS poses multiple challenges for identification of functional mutations and candidate genes. We devolopped a web server named mirTrios to accurately detect de novo mutations (DNMs) based on Expectation-maximization […]