Brazilian family with pure autosomal dominant spastic paraplegia maps to 8q: Analysis of muscle beta 1 syntrophin
✍ Scribed by Rocco, P. ;Vainzof, M. ;Froehner, S.C. ;Peters, M.F. ;Marie, S.K.N. ;Passos-Bueno, M.R. ;Zatz, M.
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 49 KB
- Volume
- 92
- Category
- Article
- ISSN
- 0148-7299
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✦ Synopsis
The autosomal dominant hereditary spastic paraplegias (AD-HSP) are a heterogeneous group of degenerative disorders of the central motor system, characterized by progressive spasticity of the lower limbs. Five loci for pure AD-HSP have been identified to date: SPG3 at 14q, SPG4 at 2p, SPG6 at 15q, SPG8 at 8q, and more recently SPG10 at 12q. We have analyzed a Brazilian family with 16 affected individuals by pure AD-HSP who developed progressive gait disturbance with onset at age 18-26 years. Linkage analysis performed with 13 relatives (6 affected and 7 normal) excluded SPG3, SPG4, and SPG6 as candidate regions. However, positive LOD scores were obtained with markers flanking the candidate region for the SPG8 locus [maximum two point Lod score (Zmax) = 3.3 at theta = 0 for D8S1804]. In this region lies the syntrophin beta 1 gene (SNT2B1), a widely expressed dystrophin-associated protein and therefore a good positional and functional candidate for this disease. Immunohistochemical and Western Blot (WB) studies showed that the distribution, expression, and apparent molecular weight of the beta 1 syntrophin protein were comparable to those of normal control individuals. Therefore, it is unlikely that defects in this protein are related to SPG8, at least in the present family. Am.