Huntington's disease-like 2: a clinical, pathological, and molecular comparison to Huntington's disease

Huntington's disease-like 2 (HDL2) is a recently described disorder caused by a CTG/CAG expansion mutation on chromosome 16q24.3. Like Huntington's disease (HD), it is an adult onset, progressive, neurodegenerative autosomal dominant disorder clinically characterized by abnormal movements, dementia, and psychiatric syndromes. Almost all known affected individuals are of African ancestry. Pathologically, it is very similar to HD, with prominent cortical and striatal atrophy and intranuclear inclusions. Most surprisingly, however, the available evidence suggests that it is not a polyglutamine disease. Rather, the repeat expansion is located within junctophilin-3 in the CTG orientation. Here we review the clinical, pathological, and molecular features of HDL2 in comparison with HD, and speculate about how the distinct mutations of these disorders lead to such similar clinical and pathological phenotypes. (C) 2003 Elsevier B.V. All rights reserved.