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A Novel Deletion in SMPX Causes a Rare form of X ‐Linked Progressive Hearing Loss in Two Families Due to a Founder Effect
Author(s) -
Abdelfatah Nelly,
Merner Nancy,
Houston Jim,
Benteau Tammy,
Griffin Anne,
Doucette Lance,
Stockley Tracy,
Lauzon Julie L.,
Young TerryLynn
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22205
Subject(s) - biology , genetics , frameshift mutation , haplotype , hearing loss , stop codon , nonsense mutation , proband , nonsense mediated decay , genetic screen , mutation , allele , mutant , gene , missense mutation , rna splicing , medicine , rna , audiology
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 c DNA of a lymphoblastoid cell line, suggesting that the mutant allele may not be degraded via nonsense‐mediated m RNA 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.