Fanconi anemia (FA) is a rare syndrome characterized by bone marrow failure, malformations, and cancer predisposition. Chromosome fragility induced by DNA interstrand crosslink (ICL)-inducing drugs is the gold standard diagnostic test for FA. We present data from 198 chromosome fragility tests and propose a new chromosome fragility index that provides a cut-off diagnostic level to […]
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TMEM70 mutations are a common cause of nuclear encoded ATP synthase assembly defect: further delineation of a new syndrome
Complex V of the respiratory chain (also termed ATP Synthase) is the final step in this process cellular energy production in the form of ATP molecules. TMEM70 gene defects were recently shown to cause ATP synthase deficiency in several patients of gypsy origin. In this study we describe six Israeli patients caused by four novel […]
The inversa type of recessive dystrophic epidermolysis bullosa is caused by specific arginine and glycine substitutions in type VII collagen
The cause of the rare inversa type of the heritable blistering disorder recessive dystrophic epidermolysis bullosa (RDEB-I) is largely unknown. In RDEB-I, patients mainly have blisters in the body flexures and trunk, as well as the mucosal membranes. To increase our knowledge about RDEB-I, we collected a series of 20 patients from the Netherlands and […]
Mosaic trisomy 13: understanding origin using SNP array
Mosaicism for trisomy of chromosome 13, the existence of normal and trisomic cells in the same individual, is a very rare syndrome in liveborns presenting with variable clinical severity. However, recent studies in IVF reveal that embryonic mosaicism is not as rare, and may also have more clinical implications than previously thought. In this study, […]
Constitutional mosaic genome-wide uniparental disomy due to diploidisation: an unusual cancer-predisposing mechanism
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 […]
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 […]