Is disomic homozygosity at the APECED locus the cause of increased autoimmunity in Down's syndrome?
Julian P H Shielda, Emma J K Wadswortha, Terry J Hassoldb, Lu Ann Judisb, Patricia A Jacobsc
a Institute of Child
Health, University of Bristol, St Michael's Hill, Bristol BS2 8BJ, UK, b Department of Genetics and the Centre for Human
Genetics, Case Western Reserve University School of Medicine, and the
University Hospital, Cleveland, OH 44106, USA, c Wessex Regional Genetics
Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UK
Correspondence to: Dr Shield. email: J.P.H.Shield{at}bris.ac.uk
Accepted 3 March 1999
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.
METHODSChildren 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.
RESULTSChildren 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.
CONCLUSIONSThe
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.
Keywords: autoimmune polyglandular disease type 1 locus; Down's syndrome; insulin dependent diabetes mellitus
© 1999 by Archives of Disease in Childhood
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