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 […]
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 […]
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 […]
Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes
Recessive mutations that disable cadherin 23, a protein encoded by CDH23, cause type 1 Usher syndrome (USH1D), which is characterized by deafness, vestibular dysfunction and vision loss due to retinitis pigmentosa. However, some milder mutations of CDH23 cause deafness alone (DFNB12). The clinical presentation in individuals that have one DFNB12 mutation in combination with one […]
Studying the epigenome using next generation sequencing
Genetic information is stored in DNA, which is a string of four nucleotides (i.e. adenine, thymine, guanine and cytosine). DNA is not a linear molecule; it is wrapped around a nucleosome which is composed of histone proteins. Conventionally, the information stored in DNA is expressed through a process known as transcription when the transcriptional factor […]
Mitochondrial DNA polymerase γ mutations: an ever expanding molecular and clinical spectrum
Deficiency of DNA polymerase gamma can compromise mitochondrial DNA synthesis and has been implicated in a variety of complex autosomal recessive and autosomal dominant mitochondrial disorders, affecting both children and adults. We sequenced the exons and proximal intronic regions of the POLG gene from 2,697 independent patients and made definitive molecular diagnosis for 95 of […]
Studying the epigenome using next generation sequencing
Genetic information is stored in DNA, which is a string of four nucleotides (i.e. adenine, thymine, guanine and cytosine). DNA is not a linear molecule; it is wrapped around a nucleosome which is composed of histone proteins. Conventionally, the information stored in DNA is expressed through a process known as transcription when the transcriptional factor […]