Clinical characteristics of adolescent cases with Type A insulin resistance syndrome caused by heterozygous mutations in the β-subunit of the insulin receptor (INSR) gene
Clinical characteristics of adolescent cases with Type A insulin resistance syndrome caused by heterozygous mutations in the β-subunit of the insulin receptor (INSR) gene
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DOI：
10.1111/1753-0407.12797
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发表时间：
2019-01-01
影响因子：
4.5
通讯作者：
Morio, Tomohiro
中科院分区：
文献类型：
--
作者：
Takasawa, Kei;Tsuji-Hosokawa, Atsumi;Morio, Tomohiro
背景资料：A型胰岛素抵抗（IR）是一种罕见的严重先天性IR，通常由胰岛素受体（INSR）基因的杂合突变引起。虽然A型IR需要从糖尿病的早期阶段进行适当的干预，这种疾病的正确诊断是具有挑战性的，积累的情况下，详细的临床资料和基因型是required.Methods：在此，我们报告6个青春期周围的患者临床诊断为A型IR，包括4例患者与一个确定的INSR突变。为明确INSR突变导致的A型IR的临床特征，我们通过与INSR突变阴性患者的比较，验证INSR突变的A型IR患者的临床特征。结果：在INSR β亚基中检测到4个杂合错义突变：Gly1146Arg、Arg1158Trp、Arg1201Trp和1个新的Arg1201Pro突变。INSR突变所致的A型IR与其他因素所致的A型IR在临床表型上除正常脂代谢和常染色体显性遗传外无明显差异。然而，我们的分析表明，在胎儿期生长迟缓的程度与胰岛素信号传导importance.Conclusions的严重程度相关：本研究详细介绍了4例患者的临床特征与遗传学证实的A型IR。进一步积累的遗传学证实的情况下，并在早期诊断的长期治疗后，需要进一步阐明这种疾病的动力学。
Background: Type A insulin resistance (IR) is a rare form of severe congenital IR that is frequently caused by heterozygous mutations in the insulin receptor (INSR) gene. Although Type A IR requires appropriate intervention from the early stages of diabetes, proper diagnosis of this disease is challenging, and accumulation of cases with detailed clinical profiles and genotypes is required.Methods: Herein we report on six peripubertal patients with clinically diagnosed Type A IR, including four patients with an identified INSR mutation. To clarify the clinical features of Type A IR due to INSR mutation, we validated the clinical characteristics of Type A IR patients with identified INSR mutations by comparing them with mutation-negative patients.Results: Four heterozygous missense mutations within the beta-subunit of INSR were detected: Gly1146Arg, Arg1158Trp, Arg1201Trp, and one novel Arg1201Pro mutation. There were no obvious differences in clinical phenotypes, except for normal lipid metabolism and autosomal dominant inheritance, between Type A IR due to INSR mutations and Type A IR due to other factors. However, our analysis revealed that the extent of growth retardation during the fetal period is correlated with the severity of insulin signaling impairment.Conclusions: The present study details the clinical features of four patients with genetically proven Type A IR. Further accumulation of genetically proven cases and long-term treatment prognoses following early diagnosis are required to further elucidate the dynamics of this disease.