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 […]

Read More…

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 […]

Read More…

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 […]

Read More…

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 […]

Read More…

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 […]

Read More…

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 […]

Read More…

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 […]

Read More…

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 […]

Read More…