Faculty of Medicine, Memorial University, St John's, Newfoundland and Labrador, Canada.
Hum Mutat. 2013 Jan;34(1):66-9. doi: 10.1002/humu.22205. Epub 2012 Oct 11.
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.
X 连锁遗传性耳聋是最罕见的遗传性耳聋类型，占所有病例的<1%。我们在纽芬兰（家族 2024）发现了一个具有 X 连锁遗传性耳聋的多态性家族。对 X 染色体的单体型分析和定位候选基因的测序揭示了 SMPX 中的一个新的点缺失（c.99delC），该基因编码一种小肌肉蛋白，负责在肌肉收缩过程中减少机械应力。这种新的缺失导致移码和过早的终止密码子（p.Arg34GlufsX47）。我们成功地从淋巴母细胞系的 cDNA 中对 SMPX 的野生型和突变等位基因进行了测序，表明突变等位基因可能不会通过无意义介导的 mRNA 降解而被降解。为了研究 SMPX 在其他亚群中的作用，我们对 229 名有听力损失的加拿大先证者进行了 SMPX 的全序列分析，发现了第二个具有相同突变的纽芬兰家族（2196），以及 X 染色体上共享的单体型，提示存在共同的祖先。
