Rinsho Shinkeigaku (Clinical Neurology)

Case Report

Familial amyotrophic lateral sclerosis (FALS) with a novel SOD1 gene mutation: A clinicopathological study

Chizuru Kawamata, M.D.1), Mitsuya Morita, M.D.1), Noriyuki Shibata, M.D.2) and Imaharu Nakano, M.D.1)

1)Department of Neurology, Jichi Medical University
2)Department of Pathology, Tokyo Women's Medical College

We describe a patient with familial amyotrophic lateral sclerosis (FALS) in whom we identified a substitution of G for CGTTTA at codon 144 in the Cu/Zn superoxide dismutase 1 (SOD1) gene, causing amino acid changes from leucine to phenylalanine, valine and a stop codon (L144FVX). This mutation is novel, and so we report the clinical and neuropathological features of this case compared with those of other FALS cases with SOD1 mutations. A 39-year-old woman developed muscle weakness and atrophy in the hands, which rapidly progressed and expanded to other muscles, resulting in respiratory insufficiency and death at only 10 months after the onset. Her grandmother, father and uncle had also been diagnosed as having ALS. The most noticeable neuropathological findings in the present case were marked loss of large motor neurons in the anterior horns associated with the frequent appearance of cord-like swollen, partially SOD1- and ubiquitin-immunopositive axons. These findings together with the absence of Bunina bodies are compatible with the neuropathology of FALS with SOD1 gene mutation, although Lewy body-like inclusions characteristic for this condition were not observed.

(CLINICA NEUROL, 47: 211－216, 2007)
key words: SOD1 gene, familial amyotrophic lateral sclerosis (FALS)

(Received: 22-Aug-06)