SNTG1, the gene encoding gamma1-syntrophin: a candidate gene for idiopathic scoliosis.

Abstract

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.

• Authors: Stavros Bashiardes, Rose Veile, Missy Allen, Carol A Wise, Mathew Dobbs, Jose A Morcuende, Lazlos Szappanos, John A Herring, Anne M Bowcock, Michael Lovett
• Journal: Human genetics (Hum Genet) Vol. 115 Issue 1 Pg. 81-9 (Jun 2004) ISSN: 0340-6717 [Print] Germany
• PMID: 15088139 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Membrane Proteins
• Nerve Tissue Proteins
• SNTG1 protein, human

Topics

• Adaptor Proteins, Signal Transducing
• Base Sequence
• Chromosome Inversion
• Chromosome Segregation
• Chromosomes, Artificial, Bacterial
• Chromosomes, Human, Pair 8
• Gene Deletion
• Humans
• In Situ Hybridization, Fluorescence
• Male
• Membrane Proteins
• Nerve Tissue Proteins (genetics)
• Pedigree
• Physical Chromosome Mapping
• Scoliosis (genetics)