A Frameshift Mutation in GRXCR 2 Causes Recessively Inherited Hearing Loss
dc.contributor.author | Imtiaz, Ayesha | en_US |
dc.contributor.author | Kohrman, David C. | en_US |
dc.contributor.author | Naz, Sadaf | en_US |
dc.date.accessioned | 2014-05-23T16:00:05Z | |
dc.date.available | WITHHELD_13_MONTHS | en_US |
dc.date.available | 2014-05-23T16:00:05Z | |
dc.date.issued | 2014-05 | en_US |
dc.identifier.citation | Imtiaz, Ayesha; Kohrman, David C.; Naz, Sadaf (2014). "A Frameshift Mutation in GRXCR 2 Causes Recessively Inherited Hearing Loss." Human Mutation 35(5): 618-624. | en_US |
dc.identifier.issn | 1059-7794 | en_US |
dc.identifier.issn | 1098-1004 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/106992 | |
dc.description.abstract | More than 360 million humans are affected with some degree of hearing loss, either early or later in life. A genetic cause for the disorder is present in a majority of the cases. We mapped a locus ( DFNB 101) for hearing loss in humans to chromosome 5q in a consanguineous P akistani family. Exome sequencing revealed an insertion mutation in GRXCR 2 as the cause of moderate‐to‐severe and likely progressive hearing loss in the affected individuals of the family. The frameshift mutation is predicted to affect a conserved, cysteine‐rich region of GRXCR 2, and to result in an abnormal extension of the C ‐terminus. Functional studies by cell transfections demonstrated that the mutant protein is unstable and mislocalized relative to wild‐type GRXCR 2, consistent with a loss‐of‐function mutation. Targeted disruption of G rxcr2 is concurrently reported to cause hearing loss in mice. The structural abnormalities in this animal model suggest a role for GRXCR 2 in the development of stereocilia bundles, specialized structures on the apical surface of sensory cells in the cochlea that are critical for sound detection. Our results indicate that GRXCR 2 should be considered in differential genetic diagnosis for individuals with early onset, moderate‐to‐severe and progressive hearing loss. We mapped a new deafness locus DFNB101 and discovered an insertion mutation in GRXCR2 as the cause of moderate‐to‐severe hearing loss in humans. The frameshift mutation was predicted to affect the conserved, cysteine‐rich domain of GRXCR2, and to result in an abnormal extension of the C‐terminus. Cell transfection experiments demonstrated that the mutant protein is unstable and mislocalized relative to the wild type GRXCR2, consistent with a loss of function mutation. | en_US |
dc.publisher | Wiley Periodicals, Inc. | en_US |
dc.publisher | The University of Michigan | en_US |
dc.subject.other | Deafness | en_US |
dc.subject.other | Progressive | en_US |
dc.subject.other | Moderate to Severe | en_US |
dc.subject.other | GRXCR 2 | en_US |
dc.subject.other | P Akistan | en_US |
dc.subject.other | DFNB 101 | en_US |
dc.title | A Frameshift Mutation in GRXCR 2 Causes Recessively Inherited Hearing Loss | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/106992/1/humu22545.pdf | |
dc.identifier.doi | 10.1002/humu.22545 | en_US |
dc.identifier.source | Human Mutation | en_US |
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dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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