Frequency of spinocerebellar ataxia type 1, dentatorubropallidoluysian atrophy, and Machado-Joseph disease mutations in a large group of spinocerebellar ataxia patients

TLDR

The spinocerebellar ataxias are a heterogeneous group of neurodegenerative disorders caused by expansions of unstable CAG repeats in several genes, including SCA1, Machado‑Joseph disease, and dentatorubropallidoluysian atrophy. We determined the frequency of the SCA1, DRPLA, and MJD mutations in a large group of unrelated SCA patients with various patterns of inheritance and different ethnic backgrounds. We studied 92 unrelated SCA patients. The study found that the MJD mutation was present in 41% of patients (17% in non‑Portuguese dominants), SCA1 in 3% overall (10% in non‑Portuguese dominants), and DRPLA in only one Japanese patient, indicating that MJD is the most common dominantly inherited SCA, SCA1 is occasionally involved, DRPLA is rare, and recessive cases are not linked to known trinucleotide expansions. NEUROLOGY 1996;46:214‑218.

Abstract

Article abstract-The spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders varying in both clinical manifestations and mode of inheritance. Six different genes causing autosomal dominant SCA are mapped: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, and dentatorubropallidoluysian atrophy (DRPLA). Expansions of an unstable trinucleotide CAG repeat cause three of these disorders: SCA type 1 (SCA1), MJD, and DRPLA. We determined the frequency of the SCA1, DRPLA, and MJD mutations in a large group of unrelated SCA patients with various patterns of inheritance and different ethnic backgrounds. We studied 92 unrelated SCA patients. The frequency of the SCA1 mutation was 3% in the overall patient group and 10% in the non-Portuguese dominantly inherited SCA subgroup. We found the DRPLA mutation in only one Japanese patient, who was previously diagnosed with this disease. We identified the MJD mutation in 41% of the overall patient group, which included 38 autosomal dominant kindreds of Portuguese origin; the frequency of the MJD mutation among the non-Portuguese dominantly inherited cases was 17%. These results suggest that SCA may be occasionally caused by the SCA1 mutation and rarely caused by the DRPLA mutation and that, to date, the MJD mutation seems to be the most common cause of dominantly inherited SCA. Finally, our results suggest that recessively inherited cases of SCA are not caused by the known trinucleotide repeat expansions. <b>NEUROLOGY 1996;46: </b> 214-218