SNTG1, the gene encoding γ1-syntrophin: A candidate gene for idiopathic scoliosis

Stavros Bashiardes, Rose Veile, Missy Allen, Carol A. Wise, Mathew Dobbs, Jose A. Morcuende, Lazlos Szappanos, John A. Herring, Anne M. Bowcock, Michael Lovett

Research output: Contribution to journalArticle

40 Scopus citations

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 γ-1 syntrophin (SNTG1) gene. Syntrophins are a group of cytoplasmic peripheral membrane proteins that associate directly with dystrophin, the Duchenne muscular dystrophy gene; γ1-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.

Original languageEnglish (US)
Pages (from-to)81-89
Number of pages9
JournalHuman genetics
Volume115
Issue number1
DOIs
StatePublished - Jun 1 2004

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Bashiardes, S., Veile, R., Allen, M., Wise, C. A., Dobbs, M., Morcuende, J. A., Szappanos, L., Herring, J. A., Bowcock, A. M., & Lovett, M. (2004). SNTG1, the gene encoding γ1-syntrophin: A candidate gene for idiopathic scoliosis. Human genetics, 115(1), 81-89. https://doi.org/10.1007/s00439-004-1121-y