Journal article
SNTG1, the gene encoding γ1-syntrophin: a candidate gene for idiopathic scoliosis
Human genetics, Vol.115(1), pp.81-89
06/01/2004
DOI: 10.1007/s00439-004-1121-y
PMID: 15088139
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; gamma 1-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.
Details
- Title: Subtitle
- SNTG1, the gene encoding γ1-syntrophin: a candidate gene for idiopathic scoliosis
- Creators
- S BashiardesR VeileMissy AllenCarol A WiseM DobbsJ A MorcuendeL SzappanosJohn A HerringA M BowcockM Lovett
- Resource Type
- Journal article
- Publication Details
- Human genetics, Vol.115(1), pp.81-89
- DOI
- 10.1007/s00439-004-1121-y
- PMID
- 15088139
- ISSN
- 0340-6717
- eISSN
- 1432-1203
- Language
- English
- Date published
- 06/01/2004
- Academic Unit
- Stead Family Department of Pediatrics; Orthopedics and Rehabilitation
- Record Identifier
- 9984040578902771
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