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 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.