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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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 […]
Combined Malonic and Methylmalonic Aciduria (CMAMMA): Exome Sequencing Reveals Mutations in the ACSF3 gene in Patients with a Non-classical Phenotype
Exome sequencing is a novel tool to find new candidate disease genes. In this report we studied two probands with the biochemical phenotype of combined elevated malonic acid (MA) and methylmalonic acid (MMA). Unlike most patients with this biochemical abnormality, our patients were asymptomatic, did not have identifiable mutations in MYLCD and had a different […]
Association of a genetic variant of BTN2A1 with metabolic syndrome in East Asian populations
This study examined the relation of rs6929846 of BTN2A1 to metabolic syndrome (MetS) in 5210 Japanese or Korean individuals from three independent subject panels. The genotype distributions and allele frequencies of rs6929846 were significantly associated with MetS in Japanese subject panels A and B, but not in Korean individuals. Multivariable logistic regression analysis revealed that […]
Patient’s perspective on the revised Ghent nosology for Mafan syndrome
On our website, every article has a Submit a Response link and the resulting e-letters are published on-line without editorial evaluation, other than checking for offensive content or copyright infringement. The feature is meant for post-publication peer-review of a scholarly nature but, occasionally, is used by members of the public—usually individuals with a stake in […]
Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch-syndrome
10-15% of patients suspected of Lynch-syndrome are mutation-negative in routine diagnostics. We identified the first paracentric inversion between the flanking genes MLH1 and LRRFIP2 flipping the genomic configuration without exonic deletion in creating two novel fusion transcripts, which even camouflaged monoallelic MLH1-deficiency when analysing only one common SNP in MLH1. Only insisting detailed analysis of […]
Identification of quantitative trait loci for murine autoimmune pancreatitis
Autoimmune pancreatitis (AIP) represents a rare but clinically relevant cause of pancreatic inflammation with largely unknown pathogenesis. Here, we have established an advanced intercross line of AIP-susceptible and resistant mouse strains to study the genetic basis of the disease. Therefore, generation G4 of outbread intercross mice was characterized phenotypically by scoring histopathological changes of the […]