Communicated by Jürgen Horst
A Novel Deletion in SMPX Causes a Rare form of X-Linked Progressive Hearing Loss in Two Families Due to a Founder Effect
Article first published online: 11 OCT 2012
© 2012 Wiley Periodicals, Inc.
Volume 34, Issue 1, pages 66–69, January 2013
How to Cite
Abdelfatah, N., Merner, N., Houston, J., Benteau, T., Griffin, A., Doucette, L., Stockley, T., Lauzon, J. L. and Young, T.-L. (2013), A Novel Deletion in SMPX Causes a Rare form of X-Linked Progressive Hearing Loss in Two Families Due to a Founder Effect. Hum. Mutat., 34: 66–69. doi: 10.1002/humu.22205
Contract grant sponsors: Canadian Foundation for Innovation (New Investigator Award no. 9384; Leaders Opportunity Fund no.13120); Canadian Institute of Health Research (CIHR 207714); Research and Development Corporation (RDC 207711); Genome Canada (Atlantic Medical Genetics and Genomics Initiative to T-L.Y.); CIHR-Regional Partnership Program (RPP) Fellowship (207716/207696 to N.A.).
- Issue published online: 20 DEC 2012
- Article first published online: 11 OCT 2012
- Accepted manuscript online: 21 AUG 2012 09:35AM EST
- Manuscript Accepted: 31 JUL 2012
- Manuscript Received: 27 APR 2012
- Canadian Foundation for Innovation. Grant Number: 9384
- Leaders Opportunity Fund. Grant Number: 13120
- Canadian Institute of Health Research. Grant Number: CIHR 207714
- Research and Development Corporation. Grant Number: RDC 207711
- CIHR-Regional Partnership Program. Grant Number: 207716/207696
- X-linked hearing loss;
- founder effect;
X-linked hearing loss is the rarest form of genetic hearing loss contributing to <1% of cases. We identified a multiplex family from Newfoundland (Family 2024) segregating X-linked hearing loss. Haplotyping of the X chromosome and sequencing of positional candidate genes revealed a novel point deletion (c.99delC) in SMPX which encodes a small muscle protein responsible for reducing mechanical stress during muscle contraction. This novel deletion causes a frameshift and a premature stop codon (p.Arg34GlufsX47). We successfully sequenced both SMPX wild-type and mutant alleles from cDNA of a lymphoblastoid cell line, suggesting that the mutant allele may not be degraded via nonsense-mediated mRNA decay. To investigate the role of SMPX in other subpopulations, we fully sequenced SMPX in 229 Canadian probands with hearing loss and identified a second Newfoundland Family (2196) with the same mutation, and a shared haplotype on the X chromosome, suggesting a common ancestor.