Cytogenetic location: 8q12 Genomic coordinates (GRCh38) : 8:54,600,001-65,100,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 8q12 | {Scoliosis, isolated, susceptibility to, 3} | 608765 | 2 |
Idiopathic scoliosis, an abnormality of the vertebral column in which patients develop lateral curvature of the spine of at least 10 degrees, affects approximately 2 to 3% of the worldwide population and has a heritable component (summary by Bashiardes et al., 2004).
For a discussion of genetic heterogeneity of isolated scoliosis, see IS1 (181800).
Bashiardes et al. (2004) described a family in which a pericentric inversion of chromosome 8 cosegregated with idiopathic scoliosis. The long arm break did not interrupt any known gene and occurred in a region of highly repetitive sequence elements. On the short arm, the break occurred in a 32-kb region between exons 10 and 11 of the SNTG1 gene (608714). Mutation analysis of SNTG1 exons in 152 sporadic idiopathic scoliosis patients revealed a 6-bp deletion in exon 10 in 1 patient and a 2-bp insertion/deletion mutation occurring in a polypyrimidine tract of intronic sequence approximately 20 bp upstream of the SNTG1 exon 5 splice site in 2 patients. These changes were not seen in a screen of 480 control chromosomes. Because SNTG1 expression appeared to be restricted to neural lineages, the authors could not directly measure SNTG1 splice forms in any of the patients.
Gao et al. (2007) studied a cohort of 52 families ascertained through probands who had received a confirmed diagnosis of idiopathic scoliosis and had reported additional family history of idiopathic scoliosis. Genomewide scans produced evidence of linkage and association with 8q12 loci (multipoint lod = 2.77; P = 0.0028). Further fine mapping in the region revealed significant evidence of disease-associated haplotypes centering over exons 2 through 4 of the CHD7 gene (608892), which had been found to be mutant in the CHARGE syndrome of multiple anomalies (214800).
For discussion of a possible association between variation in the CHD7 gene and susceptibility to idiopathic scoliosis mapping to chromosome 8q12, see 608892.0009.
Bashiardes, S., Veile, R., Allen, M., Wise, C. A., Dobbs, M., Morcuende, J. A., Szappanos, L., Herring, J. A., Bowcock, A. M., Lovett, M. SNTG1, the gene encoding gamma-1-syntrophin: a candidate gene for idiopathic scoliosis. Hum. Genet. 115: 81-89, 2004. [PubMed: 15088139] [Full Text: https://doi.org/10.1007/s00439-004-1121-y]
Gao, X., Gordon, D., Zhang, D., Browne, R., Helms, C., Gillum, J., Weber, S., Devroy, S., Swaney, S., Dobbs, M., Morcuende, J., Sheffield, V., Lovett, M., Bowcock, A., Herring, J., Wise, C. CHD7 gene polymorphisms are associated with susceptibility to idiopathic scoliosis. Am. J. Hum. Genet. 80: 957-965, 2007. [PubMed: 17436250] [Full Text: https://doi.org/10.1086/513571]