PURPOSE: 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.
CONCLUSION: IS is a multifactorial genetic disease and SH3GL1 may be one of the 
pathogenic genes for IS.