A Novel Deletion in SMPX Causes a Rare form of X-Linked Progressive Hearing Loss in Two Families Due to a Founder Effect

作者：Abdelfatah Nelly; Merner Nancy; Houston Jim; Benteau Tammy; Griffin Anne; Doucette Lance; Stockley Tracy; Lauzon Julie L; Young Terry Lynn^*

来源：Human Mutation, 2013, 34(1): 66-69.

DOI：10.1002/humu.22205

• SMPX
• X-linked hearing loss
• founder effect
• SNHL
• DFNX4

X-linked hearing loss is the rarest form of genetic hearing loss contributing to %26lt;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. Hum Mutat 34:66-69, 2013.

• 出版日期2013-1