A large Japanese SPG4 family with a novel insertion mutation of the SPG4 gene: a clinical and genetic study

We studied a large Japanese family with autosomal dominant pure hereditary spastic paraplegia (ADPHSP) clinically and genetically. To date, seven loci causing ADPHSP have been mapped to chromosomes 14q, 2p, 15q, 8q, 12q, 2q, and 19q. Among these loci, the SPG4 locus on chromosome 2p21-p22 has been s hown to account for approximately 40% of all autosomal dominant hereditary spastic paraplegia (ADHSP) families. Very recently, Hazan ct al. identified the SPG4 gene encoding a new member of the AAA (ATPases associated with di verse cellular activities) protein family, named spastin. We found a novel insertion mutation (nt1272-1273insA) in exon 8 of the SPG4 gene in the pres ent family. Our study is the first to confirm the causative mutation of the SPG4 gene in Japanese. Clinically, it is noteworthy th;lt the disease prog ression in the patients of this family was slow in spite of the late onset, and more than half of the patients showed severe constipation in addition to pure spastic paraplegia. (C) 2001 Elsevier Science B.V. All rights reser ved.