ESPE Abstracts

Background: Genes in the HLA region confer about 50% of the genetic risk of type 1 diabetes (T1DM). More than 40 different genes give a minor contribution to T1DM risk, some of them are related to the immune function.

Case presentation: A girl was referred at the age of 9 months with severe ketoacidosis in T1DM at onset. Anti-insulin autoantibodies were positive. She was the only daughter of unrelated Caucasian parents, born at term by vaginal delivery. The father suffered from Crohn disease. She showed hypotonia, facial dysmorphia with round face, prominent forehead, upslanting palpebral fissures, deep-set eyes, midface hypoplasia, and depressed nasal bridge. Methylation analysis for Prader-Willi syndrome was negative. At the age of 3 years mild mental retardation and eczema were evident and she developed juvenile idiopathic arthritis. Hypertriglyceridemia and anti-thyroperoxidase, anti-thyroglobulin autoantibodies were first detected at the age of 16 years, but thyroid function remained normal over time. She manifested growth retardation and pubertal delay with low bone mineral density and three fractures from mild trauma. Spontaneous menarche occurred at the age of 17 years. Final height was 154 cm (−1.7 SDS), significantly lower than mid-parental height (165 cm, 0.2 SDS). Recurrent seizures first appeared at the age of 16 years. CGH-array analysis showed a complex rearrangement involving chromosome 2q deletion and chromosome 10p duplication (2q37.3 (238.525.260–243.041.364) ×1, 10p15.3p14 (148.206–6.633.649) ×3).

Conclusion: Analysis of 2q and 10p regions revealed that PDCD1 (programmed cell death one precursor) gene is located on chromosome 2, while IL-2RA (interleukin two receptor, alpha chain precursor/CD25) gene is located on chromosome 10. They are involved in the regulation of T cell function during immunity and tolerance. Duplication or deletion could be responsible for changes in T regulatory cells affecting their ability to suppress effector T cell function, finally increasing susceptibility for autoimmune diseases.