Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by progressive development of fluid-filled cysts in both kidneys. Cyst formation causes chronic renal failure beyond mid-life eventually leading to end-stage renal failure. Heterozygous mutations in the polycystic kidney disease 1 (PKD1) gene and polycystic kidney disease 2 (PKD2) gene account for almost all cases and although […]
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Linkage and association analyses of glaucoma related traits in a large pedigree from a Dutch genetically isolated population
Despite extensive research on the genetic determinants of glaucoma, the genes identified to date explain only a small proportion of cases in the general population. We performed genome-wide linkage and association analyses of many glaucoma-related quantitative traits. We identified a new region of significant linkage supported by association on chromosome 20p13 (near the SIRPA and […]
CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women
A mutation in the CHEK2 gene causes a 2-fold increased breast cancer risk in female heterozygous carriers. We identified patients from breast cancer families that carried a CHEK2 mutation in both alleles (homozygous). These women have a high breast cancer risk and in addition a severe phenotype with bilateral breast cancer and multiple primary tumours. […]
Genetic basis of pain variability: recent advances
From one person to another, or one mouse strain to another, there is substantial variation in individual reporting of pain intensity and frequency as well as in behaviors indicative of pain. Genetics are responsible for some of this variability: some people inherit genetic mutations that drastically affect the protein made by the gene and make […]
Sex differences in reproductive fitness contribute to preferential maternal transmission of 22q11.2 deletions
22q11.2 deletion syndrome (22q11.2DS) is one of the most common genetic syndromes in humans. For the first time in history, most with 22q11.2DS are living to adulthood, and there is a 1 in 2 chance of passing on the condition to a child. We compared the number of children born to adults with 22q11.2DS with the […]
Histone acetylation deficits in lymphoblastoid cell lines from patients with Rubinstein–Taybi syndrome
Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder associated to mental retardation and caused by mutations in the genes CREBBP and EP300 encoding for the transcriptional regulators CBP and p300, respectively. These proteins regulate the acetylation state of the chromatin and consequently affect gene expression. Previous studies have shown that neuronal histone acetylation is reduced in […]
Patients with a phenotype consistent with facioscapulohumeral muscular dystrophy display genetic and epigenetic heterogeneity
Some patients presenting with symptoms resembling facioscapulohumeral dystrophy (FSHD) do not harbour the typical D4Z4 repeat contraction on chromosome 4q35. We investigated the genetic defect in 16 such patients and identified one patient carrying a complex rearrangement in the FSHD locus which could not be identified by standard analysis, one patient had somatic mosaicism for […]
Int22h-1/int22h-2-mediated Xq28 rearrangements: intellectual disability associated with duplications and in utero male lethality with deletions
A novel microduplication in chromosome Xq28 was identified by comparative genomic hybridization in four cognitively impaired males who share behavioral abnormalities and characteristic facial features. These duplications occur as a result of unequal exchange between two homologous regions, int22h-1 and int22h-2, which, in addition to int22h-3, are also responsible for inversions disrupting the factor VIII […]
Genetic diagnosis of Duchenne muscular dystrophy using next-generation sequencing technology: comprehensive mutational search in a single platform
Next generation sequencing technology(NGS) can be a useful tool for genetic diagnosis of certain diseases where laborious sequencing efforts are required because of the large gene size or the presence of multiple causative genes. We considered Duchenne/Becker muscular dystrophy as a suitable candidate disease for this purpose because the complex mutational spectrum and large size […]
Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers
This study identified a novel hereditary cancer syndrome caused by a germline mutation in BAP1 gene. The BAP1 mutation predisposes patients to develop uveal (ocular) melanoma, lung carcinoma, meningioma and possibly other cancers most importantly, skin melanoma and mesothelioma. The results also suggest that the frequency of germline BAP1 mutation is rather small in uveal […]