Improving diagnosis of Huntington's disease by analysis of an intragenic trinucleotide repeat expansion

Abstract

Objective: To develop an accurate presymptomatic test for Huntington's disease.

Method: An improved polymerase chain reaction method was used to investigate the pattern of expansions of a CAG repeat sequence located in the 5' region of a gene recently found to produce the protein called Huntingtin. We documented the range of trinucleotide repeat expansions in the responsible gene in 82 affected individuals compared with 80 control subjects from a Western Australian population.

Results: The number of expanded repeats ranged from 40 to 73 in affected individuals and from 13 to 38 in normal controls.

Conclusions: Polymerase chain reaction analysis of a CAG repeat sequence in the Huntington's disease gene clearly differentiated between normal and mutated alleles, providing an accurate diagnostic test for the disorder in individuals at risk. This predictive test has met with greater acceptance and demand than methods using family based linkage studies.