PT - JOURNAL ARTICLE AU - Guangqian Xing AU - Jun Yao AU - Chunyu Liu AU - Qinjun Wei AU - Xuli Qian AU - Lingxin Wu AU - Yajie Lu AU - Xin Cao TI - <em>GPRASP2</em>, a novel causative gene mutated in an X-linked recessive syndromic hearing loss AID - 10.1136/jmedgenet-2016-104320 DP - 2017 Jun 01 TA - Journal of Medical Genetics PG - 426--430 VI - 54 IP - 6 4099 - http://jmg.bmj.com/content/54/6/426.short 4100 - http://jmg.bmj.com/content/54/6/426.full SO - J Med Genet2017 Jun 01; 54 AB - 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&gt;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.