A New Dominant Spinocerebellar Ataxia Linked to Chromosome 19q13.4-qter

Abstract

THE HEREDITARY ataxias are a heterogeneous group of disorders characterized by slowly progressive incoordination of gait and poor coordination of hand and eye movements, associated with degeneration of the cerebellar cortex and spinal pathways. The hereditary ataxias can be subdivided by inheritance pattern, clinical differences, and pathologic findings.^1-3 With increasing gene discovery, a molecular classification system has replaced the clinical one.⁴ The descriptive term spinocerebellar ataxia (SCA) is used to denote the progressive autosomal dominant entities, previously abbreviated ADCA. Molecular genetic studies have so far identified the loci responsible for SCA1 to 8 and SCA10 to 17. The most common genetic mechanism implicated in the etiology of SCAs is expansion of trinucleotide repeat sequences that leads to elongated polyglutamine tracts in the respective proteins. The SCAs are distinguished from the dominantly inherited episodic ataxias EA1 and EA2, which result from point mutations in ion channels, and dentatorubral-pallidoluysian atrophy, a disorder with a more complex phenotype. Two additional autosomal dominant complex disorders involving cerebellar ataxia have been identified. One of these disorders, sensory and motor neuropathy with ataxia, is characterized primarily by sensory ataxia, but affected individuals also have evidence of a motor neuropathy.⁵ Sensory and motor neuropathy with ataxia maps to chromosome 7q22.32. The other disorder, ataxia/pancytopenia, has prominent hematologic manifestations; this gene has not yet been localized.⁶