Background: A substantial amount of nuclear genes have been identified to be implicated in genetic hearing loss, while X-linked hearing loss is genetically heterogeneous and relatively infrequent.
Objective: To identify the causative gene mutation in a five-generation Chinese family with an X-linked recessive syndromic hearing loss (SHL).
Methods: Targeted X-chromosome exome sequencing was conducted, and cosegregation analysis was performed in the members of the affected family. The in silico and expression studies were also performed.
Results: A 2-bp missense mutation (c.1717_1718GC>AA, p.A573N) in the G protein-coupled receptor associated sorting protein 2 (GPRASP2) gene was identified in four hemizygous male patients and two heterozygous female carriers, which was cosegregated with the clinical phenotypes in this family. In silico analysis supported that this gene mutation is functionally deleterious, and it was detected that homologous Gprasp2 was highly expressed in multiple structures of the mouse cochlea, which suggested that GPRASP2 might be the genetic cause for the described disease phenotypes.
Conclusions: This study presented a novel X-linked SHL combined with unique and unrecognised clinical features, and a missense variation of GPRASP2 was first identified to be implicated in X-linked SHL.
Keywords: Clinical genetics; Genetic screening/counselling; Genetics; Molecular genetics.
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