title: Epidemiological survey of idiopathic scoliosis and sequence alignment analysis of multiple candidate genes.
abstract: OBJECTIVE
  To investigate the effects of genetic factors on idiopathic scoliosis (IS) and genetic modes through genetic epidemiological survey on IS in Chongqing City, China, and to determine whether SH3GL1, GADD45B, and FGF22 in the chromosome 19p13.3 are the pathogenic genes of IS through genetic sequence analysis.
  
  
  METHODS
  214 nuclear families were investigated to analyse the age incidence, familial aggregation, and heritability. SH3GL1, GADD45B, and FGF22 were chosen as candidate genes for mutation screening in 56 IS patients of 214 families. The sequence alignment analysis was performed to determine mutations and predict the protein structure.
  
  
  RESULTS
  The average age of onset of 10.8 years suggests that IS is a early onset disease. Incidences of IS in first-, second-, third-degree relatives and the overall incidence in families (5.68%) were also significantly higher than that of the general population (1.04%). The U test indicated a significant difference, suggesting that IS has a familial aggregation. The heritability of first-degree relatives (77.68 ±10.39%), second-degree relatives (69.89 ±3.14%), and third-degree relatives (62.14 ±11.92%) illustrated that genetic factors play an important role in IS pathogenesis. The incidence of first-degree relatives (10.01%), second-degree relatives (2.55%) and third-degree relatives (1.76%) illustrated that IS is not in simple accord with monogenic Mendel's law but manifests as traits of multifactorial hereditary diseases. Sequence alignment of exons of SH3GL1, GADD45B, and FGF22 showed 17 base mutations, of which 16 mutations do not induce open reading frame (ORF) shift or amino acid changes whereas one mutation (C→T)occurred in SH3GL1 results in formation of the termination codon, which induces variation of protein reading frame. Prediction analysis of protein sequence showed that the SH3GL1 mutant encoded a truncated protein, thus affecting the protein structure.
  
  
  CONCLUSIONS
  IS is a multifactorial genetic disease and SH3GL1 may be one of the pathogenic genes for IS.
authors.affiliation: Department of Orthopaedic, Southwest Hospital, Third Military University, No. 30 Gaotanyanzhengjie RAOD, Shapingba District, Chongqing, 400038, China. y07yxy1998@126.com
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Quanzhang
authors.initials: Q
authors.lastname: Jia
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xu
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.forename: Zehua
authors.initials: Z
authors.lastname: Zhang
authors.forename: Tianyong
authors.initials: T
authors.lastname: Hou
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002681:China / Q000453:epidemiology; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D017720:Molecular Epidemiology; D009679:Nuclear Family; D012600:Scoliosis / Q000453:epidemiology* / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods*; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C105159:SH3GL1 protein, human