Beckwith-Wiedemann syndrome (BWS) is one of the commonest syndromes associated to overgrowth. It is caused, in ~10-15% of cases, by a complex mechanism called “paternal uniparental disomy (UPD)”, meaning the inheritance of two paternally derived copies of part of chromosome 11 instead of one copy from each parent. UPD may lead to loss of heterozygosity […]
Category: Uncategorized
Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair
Xeroderma pigmentosum (XP) is a rare, inherited disorder of defective DNA repair, which can offer insights into the mechanism of cancer development and neurologic degeneration. This long-term study of 106 XP patients at the National Institutes of Health found a 10,000-fold increase in non-melanoma skin cancer (NMSC) and a 2,000-fold increase in melanoma following sun […]
Colorectal cancer susceptibility loci on chromosome 8q23.3 and 11q23.1 as modifiers for disease expression in lynch syndrome
Lynch syndrome confers a high lifetime risk of developing cancer, especially colorectal and endometrial cancer. Recently, six genomic regions have been identified that increase colorectal cancer (CRC) risk in the general population and two of these regions are associated with an increased risk of developing CRC in Lynch syndrome patients. The results of this study […]
Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB
Disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling causes pulmonary alveolar proteinosis (PAP) characterized by excessive accumulation of surfactant in the lung. To date, adult-onset congenital PAP has not been reported. We found the first adult-onset patient with GM-CSF-Rβc deficiency, diagnosed as PAP pathologically at age 36. She had diminished GM-CSF-dependent signaling and functions in leukocytes […]
Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy
Otto et al. describe a next generation sequencing strategy to identify mutations in 120 patients affected with a rare cystic kidney disease. The strategy employed involves pooling the DNA of 24 patients, amplyfiying the exons (376) of 18 implicated genes, and next-generation sequence analysis. The strategy is quite specific and successful, confirming 92% of mutations […]
Genetic architecture of open-angle glaucoma and related determinants
Open-angle glaucoma (OAG) is a major sight-threatening disease worldwide. For long, only rare variants implicated in familial forms were known, but recently common variants were discovered. This raises the question whether OAG is genetically determined by many rare major mutations or also by multiple common variants (i.e. a polygenic model). In this study, genome-wide common […]
GeneScreen: a program for high-throughput mutation detection in DNA sequence electropherograms
As DNA sequencing technology has improved over recent years, operator time has become the rate-limiting factor for mutation detection and error checking, and hence a large determinant of the cost of mutation analysis. GeneScreen is a new desktop computer programme that facilitates rapid analysis of large batches of capillary electropherograms, identifying sequence variants for operator […]
Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability
Cerebral palsy (CP), the most common physical disability of childhood, is a group of neurodevelopmental disorders of movement and posture often associated with cognitive and behavioral disturbances. Although CP has been attributed to several factors, the cause of most cases remains unknown. Birth asphyxia, long considered the most frequent risk factor, accounts for <10% of […]
Uptake of breast cancer prevention and screening trials
Evans et al publish figures again showing disappointingly low recruitment rates of women at high risk of breast cancer to prevention trials. Of 4359 women invited to 5 different drug or dietary prevention trials only 5-13% decided to join the study concerned. In contrast uptake to two mammography screening trials was >95%. If we are […]
Variants in CFTR untranslated regions are associated with congenital bilateral absence of the vas deferens
Dysfunctions of the Cystic Fibrosis Transmembrane conductance regulator (CFTR) gene are responsible for the highly variable clinical presentation ranging from severe Cystic Fibrosis to male infertility due to congenital bilateral absence of the vas deferens (CBAVD). Despite extensive scanning, a small proportion of the CFTR mutations remains unidentified. We performed the functional analyses of a […]