Clinical and molecular analysis of 11 Sicilian SCA2 families: influence ofgender on age at onset

Autosomal dominant cerebellar ataxias (ADCAs) are a complex group of slowly progressive neurodegenerative disorders characterized by gait and stance a taxia, dysarthria and other symptoms of nervous system involvement. ADCA ty pe I is the commonest form and is genetically heterogeneous; several loci h ave been identified, Spinocerebellar ataxia type 2 (SCA2) has been mapped t o chromosome 12, with expanded cytosine-adenine-guanine (CAG) repeats being identified as the mutational cause of the disease. We investigated 15 fami lies, all originating from mid-eastern Sicily, with ADCA type I; molecular studies performed in 12 families showed the SCA2 mutation to be present in 11 of them (91.6%) - the highest occurrence so far reported in the literatu re, The CAG repeat of the affected alleles varied between 34 and 44 repeats , Age at onset and repeat length revealed an inverse correlation. Mean age at onset was 37.32 +/- 16.74 years, and occurred earlier in males than in f emales. There were no differences in mean CAG repeat units between the sexe s, However, a higher instability of CAG repeats was observed for paternal t ransmission than for maternal transmission. Age at onset and anticipation w ere not related to parental transmission, Our data suggest that in SCA2 an unknown sex-linked factor may play a role in the modulation of toxic effect s of the polyglutamine tract, Eur J Neurol 6:301-307 (C) 1999 Lippincott Wi lliams & Wilkins.