title: Permanent neonatal diabetes mellitus due to a C96Y heterozygous mutation in the insulin gene. A case report.
abstract: 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.
authors.affiliation: Department of Endocrinology, Amrita Institute of Medical Sciences, Cochin, India.
authors.forename: Anish
authors.initials: A
authors.lastname: Ahamed
authors.forename: Ambika Gopalakrishnan
authors.initials: AG
authors.lastname: Unnikrishnan
authors.forename: Sanket Sharad
authors.initials: SS
authors.lastname: Pendsey
authors.forename: Sheela
authors.initials: S
authors.lastname: Nampoothiri
authors.forename: Nisha
authors.initials: N
authors.lastname: Bhavani
authors.forename: Valliyaparambil Pavithran
authors.initials: VP
authors.lastname: Praveen
authors.forename: Harish
authors.initials: H
authors.lastname: Kumar
authors.forename: Rohinivilasam Vasukutty
authors.initials: RV
authors.lastname: Jayakumar
authors.forename: Vasantha
authors.initials: V
authors.lastname: Nair
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Emma L
authors.initials: EL
authors.lastname: Edghill
mesh_terms: 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
chemical_list: D007328:Insulin