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 C→T) 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.