Unknown

Dataset Information

0

Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82.

ABSTRACT: Massively parallel sequencing of targeted regions, exomes, and complete genomes has begun to dramatically increase the pace of discovery of genes responsible for human disorders. Here we describe how exome sequencing in conjunction with homozygosity mapping led to rapid identification of the causative allele for nonsyndromic hearing loss DFNB82 in a consanguineous Palestinian family. After filtering out worldwide and population-specific polymorphisms from the whole exome sequence, only a single deleterious mutation remained in the homozygous region linked to DFNB82. The nonsense mutation leads to an early truncation of the G protein signaling modulator GPSM2, a protein that is essential for maintenance of cell polarity and spindle orientation. In the mouse inner ear, GPSM2 is localized to apical surfaces of hair cells and supporting cells and is most highly expressed during embryonic development. Identification of GPSM2 as essential to the development of normal hearing suggests dysregulation of cell polarity as a mechanism underlying hearing loss.

SUBMITTER: Walsh T 

PROVIDER: S-EPMC2896776 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82.

Walsh Tom T   Shahin Hashem H   Elkan-Miller Tal T   Lee Ming K MK   Thornton Anne M AM   Roeb Wendy W   Abu Rayyan Amal A   Loulus Suheir S   Avraham Karen B KB   King Mary-Claire MC   Kanaan Moien M  

American journal of human genetics 20100617 1

Massively parallel sequencing of targeted regions, exomes, and complete genomes has begun to dramatically increase the pace of discovery of genes responsible for human disorders. Here we describe how exome sequencing in conjunction with homozygosity mapping led to rapid identification of the causative allele for nonsyndromic hearing loss DFNB82 in a consanguineous Palestinian family. After filtering out worldwide and population-specific polymorphisms from the whole exome sequence, only a single  ...[more]

Similar Datasets

Unknown Homozygosity mapping reveals mutations of GRXCR1 as a cause of autosomal-recessive nonsyndromic hearing impairment.
| S-EPMC2820176 | biostudies-literature
Unknown Whole-exome sequencing identifies MYO15A mutations as a cause of autosomal recessive nonsyndromic hearing loss in Korean families.
| S-EPMC3727941 | biostudies-literature
Unknown Homozygosity mapping and candidate prioritization identify mutations, missed by whole-exome sequencing, in SMOC2, causing major dental developmental defects.
| S-EPMC3234372 | biostudies-literature
Unknown Whole-exome sequencing efficiently detects rare mutations in autosomal recessive nonsyndromic hearing loss.
| S-EPMC3511533 | biostudies-literature
Unknown SNP linkage analysis and whole exome sequencing identify a novel POU4F3 mutation in autosomal dominant late-onset nonsyndromic hearing loss (DFNA15).
| S-EPMC3832514 | biostudies-literature
Unknown Identification of copy number variants through whole-exome sequencing in autosomal recessive nonsyndromic hearing loss.
| S-EPMC4150376 | biostudies-literature
Unknown Whole-exome sequencing identifies two novel mutations in KCNQ4 in individuals with nonsyndromic hearing loss.
| S-EPMC6226507 | biostudies-literature
Unknown Exome sequencing identifies a mutation in TMC1 as a novel cause of autosomal recessive nonsyndromic hearing loss.
| S-EPMC4731951 | biostudies-literature
Unknown Homozygosity mapping and whole exome sequencing reveal a novel homozygous COL18A1 mutation causing Knobloch syndrome.
| S-EPMC4231049 | biostudies-literature
Unknown GPSM2 mutations cause the brain malformations and hearing loss in Chudley-McCullough syndrome.
| S-EPMC3370271 | biostudies-literature