Huntington’s disease in the Maltese islands and frequencies of trinucleotide repeats

Abstract

Huntington’s disease is an autosomal dominant progressive neurological condition characterised by involuntary movements and dementia. It is caused by an expansion of trinucleotide repeats (CAG)n in the Huntington gene. This paper reviews the 123 individuals who had DNA tests for Huntington’s disease in the Maltese Islands over the period 1994 to 2003. The number of repeats in the individuals tested ranged from 10 to 64, and their relative frequencies were analysed. Two cases with unusually large expansions of over 60 repeats were juvenile cases, which occurred in boys with onset of symptoms in at puberty or adolescence and characteristic behaviour patterns. The correlation between age of onset of symptoms and the number of (CAG)n repeats was analysed. The proportion of cases in which the number of repeats increased from one generation to the next in paternally transmitted cases was assessed. Our studies showed that whilst most cases can be traced through a number of generations, some cases with a confirmed negative family history may be the result of new mutations. The mutation in Huntington’s disease is an instability of the number of CAG)n repeats that does not manifest symptoms for a number of generations while the gene is expanding, and until it exceeds a critical number of CAG)n repeats.