HUNTINGTONS-DISEASE IN GRAMPIAN REGION - CORRELATION OF THE CAG REPEAT NUMBER AND THE AGE-OF-ONSET OF THE DISEASE

The identification of an unstable trinucleotide repeat as the mutation responsible for Huntington's disease (HD) has given the hope that add itional information can be provided about age of onset and mode of act ion of the mutated gene. We present in this paper results of a clinica l and molecular study of 82 patients affected with HD from 46 pedigree s within the Grampian region, Scotland. Our results show a correlation between age of onset and size of the CAG expansion. This study has pr oduced no overlap in mutation size between affected and unaffected all eles. The sex of the parent transmitting the mutated allele and the si ze of the normal allele have no significant effect on the clinical fea tures of the disease. In the three juvenile cases the affected parent was the father but the number of cases is too small to produce statist ical significance. An increase in the CAG repeat size is shown in the transmission of the gene in five cases, accompanied by an earlier age of onset in four; in three of these cases, the affected parent was the father. Eleven sib pairs were studied and there is a negative correla tion between the difference in age at onset and the difference in repe at size. Thus there is some evidence of a relationship, but this is no t statistically significant because of the small numbers involved. The presence of the same or different normal allele had no effect on age of onset in this small group. We suggest that additional factors, as y et unrecognised, influence the age of onset and clinical presentation of HD.