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 […]

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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. […]

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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 […]

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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 […]

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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 […]

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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 […]

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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 […]

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New findings for phenotype–genotype correlations in a large European series of holoprosencephaly cases

Holoprosencephaly (HPE) is the most common forebrain defect in humans characterized by failure of the cerebral hemispheres to completely separate into two distinct halves. The wide HPE spectrum encompasses distinct brain malformation types (from alobar HPE to microform), various craniofacial defects (from cyclopia to normal face) and other extra-craniofacial defects. In addition to this clinical […]

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