AKAP2 identified as a novel gene mutated in a Chinese family with adolescent idiopathic scoliosis.

BACKGROUND: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. OBJECTIVE:The aim of this study was to identify the causative gene in a family with adolescent idiopathic scoliosis. METHODS: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. RESULTS: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). CONCLUSIONS: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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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