SOMATIC AND GONADAL MOSAICISM OF THE HUNTINGTON DISEASE GENE CAG REPEAT IN BRAIN AND SPERM

Huntington disease is associated with an unstable and expanded (CAG) t rinucleotide repeat. We have analysed the CAG expansion in different t issues from 12 affected individuals. All tissues examined were found t o display some repeat mosaicism, with the greatest levers detected in brain and sperm. Regions within the brain showing most obvious neuropa thology, such as the basal ganglia and the cerebral cortex, displayed the greatest mosaicism, whereas the cerebellar cortex, which is seldom involved, displayed the lowest degree of CAG instability. In two case s of childhood onset disease we detected differences of 8 and 13 trinu cleotides between the cerebellum and other regions of the brain. Our r esults provide evidence for tissue specific instability of the CAG rep eat, with the largest CAG repeat lengths in affected regions of the br ain.