title: AKAP2 identified as a novel gene mutated in a Chinese family with adolescent idiopathic scoliosis.
abstract: Adolescent idiopathic scoliosis exhibits high heritability and is one of the most common spinal deformities found in adolescent populations. However, little is known about the disease-causing genes in families with adolescent idiopathic scoliosis exhibiting Mendelian inheritance.
  
  
  
  The aim of this study was to identify the causative gene in a family with adolescent idiopathic scoliosis.
  
  
  
  Whole-exome sequencing was performed on this family to identify the candidate gene. Sanger sequencing was conducted to validate the candidate mutations and familial segregation. Real-time QPCR was used to measure the expression level of the possible causative gene.
  
  
  
  We identified the mutation c.2645A>C (p.E882A) within the AKAP2 gene, which cosegregated with the adolescent idiopathic scoliosis phenotypes. AKAP2 is located in a previously reported linkage locus (IS4) on chromosome 9q31.2-q34.2 and has been implicated in skeletal development. The mutation was absent in dbSNP144, ESP6500 and 503 ethnicity-matched controls. Real-time QPCR revealed that the mRNA expression level in the patients was increased significantly compared with the family controls (p<0.0001).
  
  
  
  AKAP2 was therefore implicated as a novel gene mutated in a Chinese family with adolescent idiopathic scoliosis. Further studies should be conducted to validate the results from the perspective of both the genetics and pathogenesis of this disease.
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: YaWei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lusi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Di
authors.initials: D
authors.lastname: Tian
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Dai
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Laboratory of Prepotency and Genetics, Weihai Maternal and Child Health Hospital, Weihai, Shandong, China.
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics*; D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D002874:Chromosome Mapping; D059472:Exome / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D057182:Mendelian Randomization Analysis / Q000379:methods; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012600:Scoliosis / Q000235:genetics*
chemical_list: D054758:A Kinase Anchor Proteins; C484688:AKAP2 protein, human; D008565:Membrane Proteins
keywords: AKAP2; adolescent idiopathic scoliosis; whole-exome sequencing