Is disomic homozygosity at the APECED locus the cause of increased autoimmunity in Down's syndrome?

Aims-To insulin (IDDM) in children with Down's syndrome compared with non-t risomic individuals, and to assess whether differences might be related to disomic homozygosity at the autoimmune polyglandular disease type 1(APECED) gene locus. Methods-Children with Down's syndrome and IDDM were identified through the Down's syndrome association newsletter and from paediatricians. DNA was ext racted from mouthbrush preparations provided by the parents and patients us ing standard techniques. Mapping techniques were then used to identify area s of reduction to homozygosity, including a marker that overlaps the locus for APECED. The frequency of disomic homozygosity for all markers (n = 18) was compared with a control group of 99 patients with Downs syndrome and th eir parents. The families also answered a questionnaire concerning diabetes and related autoimmune conditions in the family. Details were compared wit h the British Paediatric Surveillance Group 1988 diabetes study. Results-Children with Down's syndrome and IDDM were diagnosed significantly earlier than the general population (6.7 upsilon 8.0 years) with a far hig her proportion diagnosed in the first 2 years of life (22% upsilon 7%). The re was no evidence of increased disomic homozygosity in the region of the A PECED locus in Down's syndrome patients with IDDM compared with simple Down 's syndrome. Conclusions-The natural history of IDDM in Down's syndrome is different fro m that of the general population. Although children with Down's syndrome ha ve features similar to cases of APECED, disomic homozygosity in this region does not explain the predilection for autoimmune disease.