Identification of 2 New Genetic Markers for Idiopathic Scoliosis

Purpose: While the genetic basis of idiopathic scoliosis (IS) is well established, clear identification of IS markers has been elusive. We searched for autosomal markers that would correlate with IS that underwent fusion for curves >40 . The development of a gene-based diagnostic and prognostic test from these results could improve IS management.

Methods: DNA was collected by blood and/or cheek swab from 500 IS probands and unaffected first degree relatives whose medical records and x-rays were examined to exclude other diagnoses. Their names were submitted to a 22 million name data base to establish familial relationships which were determined at >97%. The DNA was analyzed by capillary electrophoresis for 763 short tandem repeats and gene chip scanning for 116,000 single nucleotide polymorphisms (SNP). Disease haplotypes were also scanned with a 500K SNP chip to further narrow the position of the loci.

Summary: Two previously unreported markers were identified with cumulative LOD scores of 7.0 and 7.3 and highly significant p-values. These markers were present in 95% of those with IS >40 and were not present in unaffected family members or those with IS.

Discusison: Significant differences between AIS patients and controls were identified for several single nucleotide polymorphisms. Phenotype-genotype correlations (p<0 .001) with respect to the degree of curve are underway and data will be presented. Using information from these studies a genetic test for AIS may possible that would offer both diagnostic prognostic value. Further identification genes covered by markers lead molecular pathway which results in development IS.

Hibbs Award Nominee for Best Basic Science Paper