A Japanese SPG4 family with a novel missense mutation of the SPG4 gene: intrafamilial variability in age at onset and clinical severity

Namekawa M, Takiyama Y, Sakoe K, Nagaki H, Shimazaki H, Yoshimura M, Ikeguchi K, Nakano I, Nishizawa M. A Japanese SPG4 family with a novel missense mutation of the SPG4 gene: intrafamilial variability in age at onset and clinical severity. Acta Neurol Scand 2002: 106: 387–391. © Blackwell Munksgaard 2002. Objectives– We report the results of clinical and genetic studies on a Japanese SPG4 family. Material and methods– Family N included eight patients in four generations with autosomal dominant transmission. We performed neurological and molecular analyses on the SPG4 gene in the family members comprising three patients, 12 at-risk individuals, and three normal spouses. Results– The three patients showed pure spastic paraplegia, two of them exhibiting a decrease in vibration sense. There was marked intrafamilial variability in age at onset and clinical severity in the present family. On molecular analysis, a novel missense mutation (nt1579 CT) in exon 12 of the SPG4 gene was found in the three patients, three probably affected, and an asymptomatic carrier. Conclusion– The present SPG4 family, which was shown to have a novel SPG4 mutation, exhibited marked variability in the clinical features, indicating the participation of additional factors in the phenotypic appearance of this family.