DIFFERENTIAL PATTERN IN TISSUE-SPECIFIC SOMATIC MOSAICISM OF EXPANDEDCAG TRINUCLEOTIDE REPEAT IN DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY, MACHADO-JOSEPH DISEASE, AND X-LINKED RECESSIVE SPINAL AND BULBAR MUSCULAR-ATROPHY

We investigated the somatic mosaicism of trinucleotide repeat expansio n in the neural and nonneural tissues of a dentatorubral-pallidoluysia n atrophy (DRPLA), Machado-Joseph disease (MJD), and spinal and bulbar muscular atrophy (SBMA) patient and their correlation to the topograp hical distribution of the pathological involvement. The spatial patter n of tissue-specific somatic mosaicism in the CAG repeat size was sign ificantly different among the DRPLA, MJD and SBMA patients. The size o f the major bands of the mutant CAG repeat allele was significantly sm aller 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 DRPL A by 5 repeats or more. There were also 1-2 repeat-sized small variati ons 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 ti ssue-specific CAG instability and severity of neuropathological involv ement in the neural and nonneural tissues of DRPLA, MJD and SBMA patie nts. Lack of significant tissue-specific somatic mosaicism in SBMA inc luding the cerebellar cortex may suggest that CAG repeat expansion in the mutant androgen receptor gene is far more stable compared with tha t in DRPLA and MJD as well as those reported in Huntington's disease.