A novel deletion in SMPX causes a rare form of X-linked progressive hearing loss in two families due to a 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.
Faculty of Medicine, Memorial University, St John's, Newfoundland and Labrador, Canada.
Nelly
N
Abdelfatah
Nancy
N
Merner
Jim
J
Houston
Tammy
T
Benteau
Anne
A
Griffin
Lance
L
Doucette
Tracy
T
Stockley
Julie L
JL
Lauzon
Terry-Lynn
TL
Young
D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D018703:Founder Effect; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion
D009124:Muscle Proteins; C433890:SMPX protein, human