Epidemiological survey of idiopathic scoliosis and sequence alignment analysis of multiple candidate genes

Abstract

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%), seconddegree 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 firstdegree 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.

The publication trends and hot spots of scoliosis research from 2009 to 2018: a 10-year bibliometric analysis

“…They also show a high degree of genetic heterogeneity in autosomal dominant or multifactorial inheritance patterns with major genes. Many studies identified idiopathic scoliosis-susceptible genes (such as SH3GL1, GADD45B, and FGF22) and linked them to idiopathic scoliosis, but these genes are not to all idiopathic scoliosis cases (35)(36)(37)(38). There is no doubt that idiopathic scoliosis is a hereditary disease, so finding its related pathogenic genes is of great significance for the prevention or treatment of idiopathic scoliosis, and it must be a hot spot for future research.…”

Idiopathic scoliosis: a systematic review and meta-analysis of heritability

“…The heritability of idiopathic scoliosis has been reported in a few studies with different methodologies supporting the importance of hereditary factors ( 5 , 7 , 22 ). However, the proportion of the observed variance in idiopathic scoliosis that is attributed to genetics is highly uncertain.…”

Ultrastructure of Intervertebral Disc and Vertebra-Disc Junctions Zones as a Link in Etiopathogenesis of Idiopathic Scoliosis

“…Characteristics of the protein that is encoded by C17orf67 are not studied well [196]. Other genes SNPs that have been reported as having association with AIS are SH3GL1 [197], LAPTM4B [119], IFG1 [119], MMP9 [198], HTR1A [199], and TIMP2 [200]. Axial Biotech Inc. [202] has developed a test to identify patients with low risk of scoliotic curve progression using 53 genetic markers.…”