Linkage disequilibrium at the Machado-Joseph disease spinal cerebellar ataxia 3 locus: Evidence for a common founder effect in French and Portuguese-Brazilian families as well as a second ancestral Portuguese-Azorean mutation
- and others
Spinal cerebellar ataxia 3 (SCA3) is a genetic subtype of the type I autosomal dominant cerebellar ataxias (ADCA type I), a clinically and genetically heterogeneous group of neurological disorders. SCA3 was mapped in French families to chromosome 14q24.3-qter in the same region as the gene for Machado-Joseph disease (MJD), which was classified as a form of ADCA type I on the basis of similarities in the clinical presentation of individual patients. The MJD gene was recently identified in Japanese kindreds, and the mutation was characterized as an unstable CAG repeat that is expanded in affected individuals. The same mutation is observed in families of Portuguese-Azorean ancestry, as well as in French SCA3 kindreds. In other disorders caused by unstable and expanded triplet repeats, such as fragile X syndrome (FRA-X), myotonic dystrophy (MD), Huntington disease (HD), and SCA1, linkage disequilibrium (LD) between the mutation and closely linked polymorphic markers was detected, suggesting that there were only one or a few founders or predisposing haplotypes. In the present study, 29 families of different geographical origins were tested for LD between the MJD/SCA3 mutation and four flanking microsatellite markers. 27 refs., 2 tabs.
- OSTI ID:
- 209920
- Journal Information:
- American Journal of Human Genetics, Vol. 57, Issue 5; Other Information: PBD: Nov 1995
- Country of Publication:
- United States
- Language:
- English
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