A novel mutation in INS gene linked to permanent neonatal diabetes mellitus.
Endocrine
; 64(3): 719-723, 2019 06.
Article
in En
| MEDLINE
| ID: mdl-30915639
ABSTRACT
PURPOSE:
Neonatal diabetes mellitus (NDM) is caused by mutations in the genes responsible for pancreatic ß cell mass or function. This study aimed to screen the mutations in the KCNJ11, ABCC8, and INS genes in a Chinese patient with clinical features of NDM.METHODS:
The entire coding sequence and exon/intron boundaries of KCNJ11, ABCC8, and INS genes were detected by Sanger sequencing. The pathogenicity of the mutation was determined by using online prediction programs SIFT and Mutation Taser. The conformational alterations which contribute to the change of protein function were analyzed at the structural level.RESULTS:
A novel mutation L35Q (B11) of the INS gene was discovered in the patient. As L35 residue contributes to its hydrophobic core of the protein, the L35Q substitution is predicated to affect B19-A20 disulfide bond and therefore disrupt the folding of the proinsulin, which ultimately results in beta cell apoptosis by inducing ER stress.CONCLUSIONS:
This case could help us understand the role of the INS mutation in the development of diabetes.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diabetes Mellitus
/
Insulin
Type of study:
Prognostic_studies
Limits:
Adult
/
Humans
/
Male
Language:
En
Journal:
Endocrine
Journal subject:
ENDOCRINOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
China