Brazilian family with pure autosomal dominant spastic paraplegia maps to 8q: analysis of muscle beta 1 syntrophin.
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.
Rocco
P
P
Centro de Estudos do Genoma Humano, Department of Biology, University of Sao Paulo, São Paulo, Brazil.
Vainzof
M
M
Froehner
S C
SC
Peters
M F
MF
Marie
S K
SK
Passos-Bueno
M R
MR
Zatz
M
M
D017668:Age of Onset; D001938:Brazil; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D049029:Dystrophin-Associated Proteins; D005192:Family Health; D005260:Female; D005455:Fluorescent Antibody Technique; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D018895:Microsatellite Repeats; D009124:Muscle Proteins / Q000378:metabolism; D009132:Muscles / Q000737:chemistry / Q000473:pathology; D010264:Paraplegia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010375:Pedigree
D049029:Dystrophin-Associated Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C091824:syntrophin; D004247:DNA