title: GPRASP2, a novel causative gene mutated in an X-linked recessive syndromic hearing loss.
abstract: 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.
  
  
  
  To identify the causative gene mutation in a five-generation Chinese family with an X-linked recessive syndromic hearing loss (SHL).
  
  
  
  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.
  
  
  
  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 homologousGprasp2was highly expressed in multiple structures of the mouse cochlea, which suggested thatGPRASP2might be the genetic cause for the described disease phenotypes.
  
  
  
  This study presented a novel X-linked SHL combined with unique and unrecognised clinical features, and a missense variation ofGPRASP2was first identified to be implicated in X-linked SHL.
authors.affiliation: Department of Otolaryngology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Guangqian
authors.initials: G
authors.lastname: Xing
authors.affiliation: Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
authors.forename: Qinjun
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
authors.forename: Xuli
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Otolaryngology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Lingxin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
chemical_list: D002352:Carrier Proteins; C516849:GPRASP2 protein, human; D047908:Intracellular Signaling Peptides and Proteins
keywords: Clinical genetics; Genetic screening/counselling; Genetics; Molecular genetics