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  Next-generation sequencing identifies mutations of SMPX, which encodes the small muscle protein, X-linked, as a cause of progressive hearing impairment

Schraders, M., Haas, S. A., Weegerink, N. J., Oostrik, J., Hu, H., Hoefsloot, L. H., et al. (2011). Next-generation sequencing identifies mutations of SMPX, which encodes the small muscle protein, X-linked, as a cause of progressive hearing impairment. Am J Hum Genet, 88(5), 628-34. doi:10.1016/j.ajhg.2011.04.012.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-797E-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7980-8
Genre: Journal Article

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Schraders, M., Author
Haas, S. A., Author
Weegerink, N. J., Author
Oostrik, J., Author
Hu, H.1, Author              
Hoefsloot, L. H., Author
Kannan, S., Author
Huygen, P. L., Author
Pennings, R. J., Author
Admiraal, R. J., Author
Kalscheuer, V. M.2, Author              
Kunst, H. P., Author
Kremer, H., Author
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
2Chromosome Rearrangements and Disease (Vera Kalscheuer), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479642              

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Free keywords: Adolescent; Adult; Child; Child, Preschool; *Codon, Nonsense; DNA Mutational Analysis; Female; Frameshift Mutation; *Genes, X-Linked; Hearing Loss/*genetics/pathology; Humans; Insulin-Like Growth Factor I/genetics; Male; Middle Aged; Molecular Sequence Annotation; Muscle Proteins/*genetics; Pedigree; Polymorphism, Single Nucleotide; Sequence Analysis; Young Adult
 Abstract: In a Dutch family with an X-linked postlingual progressive hearing impairment, a critical linkage interval was determined to span a region of 12.9 Mb flanked by the markers DXS7108 and DXS7110. This interval overlaps with the previously described DFNX4 locus and contains 75 annotated genes. Subsequent next-generation sequencing (NGS) detected one variant within the linkage interval, a nonsense mutation in SMPX. SMPX encodes the small muscle protein, X-linked (SMPX). Further screening was performed on 26 index patients from small families for which X-linked inheritance of nonsyndromic hearing impairment (NSHI) was not excluded. We detected a frameshift mutation in SMPX in one of the patients. Segregation analysis of both mutations in the families in whom they were found revealed that the mutations cosegregated with hearing impairment. Although we show that SMPX is expressed in many different organs, including the human inner ear, no obvious symptoms other than hearing impairment were observed in the patients. SMPX had previously been demonstrated to be specifically expressed in striated muscle and, therefore, seemed an unlikely candidate gene for hearing impairment. We hypothesize that SMPX functions in inner ear development and/or maintenance in the IGF-1 pathway, the integrin pathway through Rac1, or both.

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 Dates: 2011
 Publication Status: Published in print
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Title: Am J Hum Genet
Source Genre: Journal
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Pages: - Volume / Issue: 88 (5) Sequence Number: - Start / End Page: 628 - 34 Identifier: ISSN: 1537-6605 (Electronic) 0002-9297 (Print)