Differential pattern in tissue-specific somatic mosaicism of expanded CAG trinucleotide repeats in dentatorubral-pallidoluysian atrophy, Machado-Joseph disease, and X-linked recessive spinal and bulbar muscular atrophy.

We investigated the somatic mosaicism of trinucleotide repeat expansion in the neural and nonneural tissues of a dentatorubral-pallidoluysian atrophy (DRPLA), Machado-Joseph disease (MJD), and spinal and bulbar muscular atrophy (SBMA) patient and their correlation to the topographical distribution of the pathological involvement. The spatial pattern of tissue-specific somatic mosaicism in the CAG repeat size was significantly different among the DRPLA, MJD and SBMA patients. The size of the major bands of the mutant CAG repeat allele was significantly smaller in the cerebellar cortex in both DRPLA and MJD patients by 6 and 2 repeat units respectively and larger in the colon and liver of DRPLA by 5 repeats or more. There were also 1-2 repeat-sized small variations of major band size among the neural tissues in DRPLA. In contrast, there was no tissue-specific variation of major bands of CAG repeats and diversity of extra bands among the examined tissues including the cerebellum in the SBMA patient. There was no parallel occurrence of tissue-specific CAG instability and severity of neuropathological involvement in the neural and nonneural tissues of DRPLA, MJD and SBMA patients. Lack of significant tissue-specific somatic mosaicism in SBMA including the cerebellar cortex may suggest that CAG repeat expansion in the mutant androgen receptor gene is far more stable compared with that in DRPLA and MJD as well as those reported in Huntington's disease.