Objective To study a large Chinese family with Type A Insulin Resistance Syndrome (TAIRS) and the members clinical phenotypes. Explore their genotype-phenotype relationship between environmental factors and hereditary features. Methods 19 members of the family were investigated for their past history, dietary habits and living habits. PCR and Sanger sequencing were applied to detect mutations of the INSR gene among 6 core members from the Pedigree. Besides, fasting blood glucose and insulin were measured or oral glucose tolerance test was performed among the 6 members. Results: (1) A heterozygous mutation C.3614C>T (p. P1205L) of the INSR gene was identified in 4 members from the core members, and the inheritance mode of the family was consistent with the autosomal dominant according to the pedigree. (2) The phenotypes of 4 members were prominently heterogeneous: the probands showed hirsutism, acanthosis nigricans, severe insulin resistance, diabetes; while the other 3 had no hirsutism or acanthosis nigricans, the father and the grandpa only showed impaired fasting glucose, while her little aunt was still healthy. (3) Phenotypic heterogeneity was associated with insulin levels, but not with environmental factors. Conclusion The C.3614C>T mutation underlies the disease in this pedigree. This mutation has not been reported in China. The gene mutation has phenotypic heterogeneity, the latter is associated with insulin levels.
Keywords: Type A Insulin Resistance Syndrome, INSR gene, Mutation, Family survey
27 - 29 Sep 2018
European Society for Paediatric Endocrinology