Permanent neonatal diabetes mellitus due to a C96Y heterozygous mutation in the insulin gene. A case report.
BACKGROUND
Neonatal diabetes is a rare disorder with an incidence of 1 in 215,000-500,000 live births with 50% of them having permanent neonatal diabetes mellitus.


METHODS
We present a case of permanent neonatal diabetes mellitus due to a C96Y (c.287G>A; p.Cys96Tyr) heterozygous mutation in the insulin (INS) gene. Both the patient and his father (who had childhood-onset insulin-requiring diabetes) were found to be carriers of a heterozygous missense mutation C96Y in exon 3 of the INS gene. It has been hypothesized that these mutations disrupt the folding of the proinsulin molecule and result in a misfolded protein or retention of the protein in the endoplasmic reticulum, resulting in endoplasmic reticulum stress and beta cell apoptosis. Subjects with this form of diabetes will need lifelong insulin therapy.


CONCLUSIONS
Insulin gene mutations appear to be an important cause of neonatal diabetes worldwide. This is the first report of a case from the Indian subcontinent. It is important to carry out genetic tests for mutations linked to pancreatic beta cell dysfunction in all patients with persistent neonatal diabetes mellitus in order to decide on therapy.
Ahamed
Anish
A
Department of Endocrinology, Amrita Institute of Medical Sciences, Cochin, India.
Unnikrishnan
Ambika Gopalakrishnan
AG
Pendsey
Sanket Sharad
SS
Nampoothiri
Sheela
S
Bhavani
Nisha
N
Praveen
Valliyaparambil Pavithran
VP
Kumar
Harish
H
Jayakumar
Rohinivilasam Vasukutty
RV
Nair
Vasantha
V
Ellard
Sian
S
Edghill
Emma L
EL
D019943:Amino Acid Substitution; D003920:Diabetes Mellitus / Q000151:congenital* / Q000188:drug therapy / Q000235:genetics*; D003937:Diagnosis, Differential; D006579:Heterozygote; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology; D007223:Infant; D007328:Insulin / Q000235:genetics* / Q000627:therapeutic use; D008297:Male
D007328:Insulin