Coexistence of expanded CAG repeats in the MJD1a and DRPLA genes.

Abstract

CAG repeat expansion is thought to be a causative genetic mutation in several neurodegenerative diseases, including Huntington’s disease; bulbospinal muscular atrophy; dentatorubral pallidoluysian atrophy (DRPLA); spinocerebellar ataxia (SCA)-1, -2, -6, and -7; and Machado–Joseph disease (MJD). It has been suggested that a common molecular mechanism might underlie the pathogenesis of these disorders, even though the CAG expansion responsible for each disease is found on different loci. To date, no cases with CAG expansions on two loci have been reported. Here, we present a case of a patient, having abnormally expanded CAG repeats both in the MJD1a and the DRPLA genes, who had neurologic symptoms at an early age. We suggest that the “gene dosage effect” might occur over different loci coding polyglutamine. ### Case report. The patient (Patient 1) is an 8-year-old boy in whom a spastic gait developed at age 6 years. He was delivered normally with a birth weight of 3200 g. His early development was said to be normal, except that his speech was delayed. Within 2 years of onset, he had manifested slurred speech, nystagmus in the …