Long repeat tracts at SCA8 in major psychosis

Expansion at a recently identified unstable trinucleotide repeat on chromos ome 13q21 has been reported as the molecular cause for spinocerebellar atax ia type 8 (SCA8). The trinucleotide repeat, which consists of a [CTA]n repe at and adjacent [CTG]n repeat, was reported to have a pathogenic range of 1 07-127 CTG: repeats (or 110-130 combined CTA and CTG repeats) in a large at axia kindred. This repeat region was also cloned by our group from a bipola r affective disorder (BPAD) patient, who has approximately 600 combined rep eats, and large alleles (>100 repeats) were reported to be present in 0.7% of controls and 1.5% of major psychosis patients (n = 710 and n = 1,120, re spectively). We have followed up these findings by screening three new samp les of BPAD and schizophrenia (SCZ) patients and controls, including 272 in dividuals from 14 BPAD families from Sweden, 130 individuals from 32 SCZ an d BPAD families/trios from the Azores Islands, and 206 SCZ individuals from the United Kingdom and Ireland, and 219 matched controls. We found large r epeat alleles above the SCA8 pathogenic range in individuals from 3 of 32 A zorean pedigrees and in 1 of 206 SCZ individuals from the United Kingdom, a nd repeat alleles within the SCA8 pathogenic range in 1 of 14 Swedish famil ies. Although the rarity of major psychosis patients carrying the SCA8 expa nsion mutation would require a much larger sample size to reach statistical significance, these results support the previously reported observation of increased occurrence of large repeats at SCA8 in major psychosis. (C) 2000 Wiley-Liss, Inc.