Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal kinesigenic choreoathetosis

Paroxysmal kinesigenic choreoathetosis (PKC), firstly reported in 1967, is characterized by recurrent and brief attacks of involuntary movement and causative gene remains unidentified. Using targeted genomic sequencing and conventional Sanger sequencing, the authors identified a spectrum of mutations in proline-rich transmembrane protein 2 (PRRT2). PRRT2 mutations cause only a subset of PKC, which suggests that […]

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Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation

Split Hand and Foot Malformation (SHFM) is a birth defect characterized by claw-like appearance of hands and feet.  Several genomic regions have been implicated in the causation of SHFM but SHFM1 is one of the most puzzling among these because despite its frequent involvement in genomic rearrangements, the compelling candidate genes DLX5/DLX6 in that region […]

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Defective NDUFA9 as a novel cause of neonatally fatal complex I disease

Mitochondrial disorders are associated with abnormalities of the oxidative phosphorylation (OXPHOS) system and cause significant morbidity and mortality in the population. The genetic cause remains still unknown in a large part of patients with mitochondrial disease. Here we report the first disease-causing mutation in the complex I subunit encoding NDUFA9 gene, which was identified in […]

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Neonatal onset Autosomal Dominant Polycystic Kidney Disease (ADPKD) in a patient homozygous for a PKD2 missense mutation due to uniparental disomy

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 […]

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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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