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


AIMS To examine the age of onset of insulin dependent diabetes mellitus (IDDM) in children with Down’s syndrome compared with non-trisomic 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 extracted from mouthbrush preparations provided by the parents and patients using standard techniques. Mapping techniques were then used to identify areas 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 Down’s syndrome and their parents. The families also answered a questionnaire concerning diabetes and related autoimmune conditions in the family. Details were compared with 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 v 8.0 years) with a far higher proportion diagnosed in the first 2 years of life (22%v 7%). There was no evidence of increased disomic homozygosity in the region of the APECED 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 from that of the general population. Although children with Down’s syndrome have features similar to cases of APECED, disomic homozygosity in this region does not explain the predilection for autoimmune disease.

  • autoimmune polyglandular disease type 1 locus
  • Down’s syndrome
  • insulin dependent diabetes mellitus

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