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.
A型胰岛素抵抗
Type A insulin resistance
insulin receptor (INSR) gene
lipodystrophy
small for gestational age (SGA)
tyrosine kinase domain
小于胎龄儿(SGA)
胰岛素受体(INSR)基因
脂肪营养不良
酪氨酸激酶结构域
Journal
Journal of diabetes
ISSN: 1753-0407
Titre abrégé: J Diabetes
Pays: Australia
ID NLM: 101504326
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
24
02
2018
revised:
02
05
2018
accepted:
01
06
2018
pubmed:
8
6
2018
medline:
8
2
2019
entrez:
8
6
2018
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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.
CONCLUSIONS
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.
Identifiants
pubmed: 29877041
doi: 10.1111/1753-0407.12797
doi:
Substances chimiques
Antigens, CD
0
INSR protein, human
EC 2.7.10.1
Receptor, Insulin
EC 2.7.10.1
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
46-54Subventions
Organisme : AMED
ID : JP17am0101111
Organisme : Japanese Society for Pediatric Endocrinology Future Development
Organisme : Novo Nordisk Pharma
Organisme : Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS))
Organisme : JSPS KAKENHI
ID : 15K19602
Organisme : Japan Agency for Medical Research and Development
Informations de copyright
© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.