LHFPL5 mutation: A rare cause of non-syndromic autosomal recessive hearing loss

Abstract

Hearing loss is a debilitating disorder that impairs language acquisition, resulting in disability in children and potential isolation in adulthood. Its onset can have a genetic basis, though environmental factors, which are often preventable, can also cause the condition. The genetic forms are highly heterogeneous, and early detection is necessary to arrange appropriate patient support. Here we report the molecular basis of hereditary hearing loss in a consanguineous family with multiple affected members from Oman. Combining homozygosity mapping with whole exome sequencing identified a novel homozygous nucleotide substitution c.575T > C in the lipoma HMGIC fusion partner-like 5 gene (LHFPL5), that converted the 192nd amino acid residue in the protein from a leucine to a proline, p.(Leu192Pro). Sanger sequencing confirmed segregation with the disease phenotype as expected for a recessive condition and the variant was absent in 123,490 subjects from various disease-specific and population genetic studies as well as 150 unrelated individuals and 35 deaf patients of Omani ethnicity. This study, which describes a novel LHFPL5 mutation in a family of Omani origin with hereditary hearing loss, supports previous clinical descriptions of the condition and contributes to the genetic spectrum of mutations in this form of deafness.