This study was performed to confirm 1) the difference in the trinucleotide CAG repeat number among tissues, 2) somatic mosaicism in each tissue, 3) the correlation of the repeat number with pathological severity in Huntington's disease. The CAG repeat number was determined by analysis of the polymerase chain reaction (PCR) product in various tissues, including central nervous system (CNS) tissues and non-CNS tissues. We also determined the pathological severity grade in each brain section and compared this with the results of CAG repeat analyses. The patient was a Japanese male with Huntington's disease who died at 62 years of age. Genomic DNA was extracted from 10 parts of the central nervous system and 6 parts of other tissues from the patient. Each part of the formalin-fixed brain was subjected to gross and microscopic pathological assessment. The main peaks of CAG repeat in all tissues were 22 and 44. In analysis of somatic mosaicism, high degrees of mosaicism were obtained in the caudate nucleus, putamen and cerebral cortex, in which more severe degeneration was observed by pathological examination. These results, although this is a single case study, indicated that pathological severity did not correlate with the CAG repeat number, but it did relate to the degree of somatic mosaicism. Somatic mosaicism might reflect region-specific neuronal degeneration in Huntington's disease.
(Internal Medicine 38: 407-411, 1999)