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Familial amyotrophic lateral sclerosis with novel A4D SOD 1 mutation with late age at onset and rapid progressive course
Author(s) -
Naruse Hiroya,
Iwata Atsushi,
Takahashi Yuji,
Ichihara Kazuaki,
Kamei Satoshi,
Yamatoku Masato,
Hirayama Toshikazu,
Suzuki Naoki,
Aoki Masashi,
Miyagawa Toji,
Shimizu Jun,
Tsuji Shoji,
Goto Jun
Publication year - 2013
Publication title -
neurology and clinical neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2049-4173
DOI - 10.1002/ncn3.8
Subject(s) - amyotrophic lateral sclerosis , mutation , medicine , age of onset , sod1 , genetics , exon , disease , genotype , pathology , biology , gene
Our objective was to obtain clinical presentations of familial amyotrophic lateral sclerosis ( FALS ) with a novel Ala4Asp (A4D) SOD 1 mutation in a Japanese family and to determine the epidemiological features of the SOD 1 mutation on the basis of the ALS mutation database. The clinical histories and neurological findings of three affected individuals in a Japanese FALS pedigree are described. DNA analysis of SOD 1 was conducted by a direct nucleotide sequence analysis. We identified a novel heterozygous A4D mutation in exon 1 in SOD 1 . The clinical presentations of the family were characterized by late age at onset and rapid progression. Comprehensive analysis of genotype‐phenotype correlations using the ALS mutation database revealed that all the patients with SOD 1 amino acid 4 mutations tended to have a rapid progressive course of the disease with a duration of 1.27 years. The age at onset varied among SOD 1 amino acid 4 mutations, but all three patients with A4D mutation had a very late age at onset of over 70 years. In conclusion, FALS patients with a novel A4D mutation in SOD 1 showed a late age at onset with a rapid disease course. This study supports the previous observations that SOD 1 amino acid 4 mutations contribute to the acceleration of disease progression and emphasizes the usefulness of the ALS mutation database.