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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.
- Source :
-
Journal of diabetes [J Diabetes] 2019 Jan; Vol. 11 (1), pp. 46-54. Date of Electronic Publication: 2018 Jul 04. - Publication Year :
- 2019
-
Abstract
- 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.<br />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.<br />Results: Four heterozygous missense mutations within the β-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.<br />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.<br /> (© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)
- Subjects :
- Acanthosis Nigricans pathology
Adolescent
Base Sequence
Child
DNA Mutational Analysis
Diabetes Mellitus pathology
Female
Heterozygote
Humans
Male
Pedigree
Severity of Illness Index
Syndrome
Acanthosis Nigricans genetics
Antigens, CD genetics
Diabetes Mellitus genetics
Insulin Resistance genetics
Mutation, Missense
Receptor, Insulin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1753-0407
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 29877041
- Full Text :
- https://doi.org/10.1111/1753-0407.12797