Idiopathic scoliosis (IS) affects approximately 2%-3% of the population and has 
a heritable component. The genetics of this disorder are complex. Here, we 
describe a family in which a pericentric inversion of chromosome 8 co-segregates 
with IS. We have used fluorescence in situ hybridization to identify cloned DNAs 
that span the breakpoints on the two arms of the chromosome. We have identified 
a bacterial artificial chromosome (BAC) of 150 kb that crosses the q-arm 
breakpoint and a BAC of 120 kb that crosses the p-arm breakpoint. The complete 
genomic DNA sequence of these BACs has been analyzed to identify candidate genes 
and to localize further the precise breakpoints. This has revealed that the 
p-arm break does not interrupt any known gene and occurs in a region of highly 
repetitive sequence elements. On the q-arm, the break occurs between exons 10 
and 11 of the gamma-1 syntrophin (SNTG1) gene. Syntrophins are a group of 
cytoplasmic peripheral membrane proteins that associate directly with 
dystrophin, the Duchenne muscular dystrophy gene; gamma1-syntrophin has been 
shown to be a neuronal cell-specific protein. Mutational analysis of SNTG1 exons 
in 152 sporadic IS patients has revealed a 6-bp deletion in exon 10 of SNTG1 in 
one patient and a 2-bp insertion/deletion mutation occurring in a polypyrimidine 
tract of intronic sequence 20 bases upstream of the SNTG1 exon 5 splice site in 
two patients. These changes were not seen in a screen of 480 control 
chromosomes. Genomic DNAs from seven affected individuals within the family of a 
patient carrying the 6-bp deletion were typed to determine whether the 
alteration co-segregated with IS. The deletion was only observed in five out of 
these seven individuals. Thus, although genetic heterogeneity or multiple 
alleles cannot be ruled out, the 6-bp deletion does not consistently 
co-segregate with the disease in this family.