title: Novel ABCC8 (SUR1) gene mutations in Asian Indian children with congenital hyperinsulinemic hypoglycemia.
abstract: Congenital hyperinsulinemic hypoglycemia (HI) is a heterogeneous genetic disorder of insulin secretion characterized by persistent hypoglycemia, most commonly associated with inactivating mutations of the β-cell ATP-sensitive K(+) channel (K(ATP) channel) genes ABCC8 (encoding SUR1) and KCNJ11(encoding Kir6.2). This study aimed to screen the mutations in the genes associated with congenital HI in Asian Indian children. Recessive mutations of these genes cause hyperinsulinism that is unresponsive to treatment with channel agonists like diazoxide. Dominant K(ATP) mutations have been associated with diazoxide-responsive disease. The KCNJ11, ABCC8, GCK, HNF4A, and GLUD1 genes were analyzed by sequence analysis in 22 children with congenital HI. We found 10 novel mutations (c.1delA, c.61delG, c.267delT, c.619-629delCCCGAGGACCT, Gln444*, Leu724Pro, Ala847Thr, Trp898*, IVS30-2A>C, and Leu1454Arg) and two known mutations (Gly111Arg and Arg598*) in the ABCC8 gene. This study describes novel and known ABCC8 gene mutations in children with congenital HI. This is the first large genetic screening study on HI in India and our results will help clinicians in providing optimal treatment for patients with hyperinsulinemia and in assisting affected families with genetic counseling.
authors.affiliation: Madras Diabetes Research Foundation, ICMR Advanced Centre for Genomics of Type 2 Diabetes and Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention & Control, IDF Centre of Education, Gopalapuram, Chennai, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Jahnavi
authors.forename: Varadarajan
authors.initials: V
authors.lastname: Poovazhagi
authors.forename: Sekar
authors.initials: S
authors.lastname: Kanthimathi
authors.forename: Kandasamy
authors.initials: K
authors.lastname: Balamurugan
authors.forename: Dhanasekaran
authors.initials: D
authors.lastname: Bodhini
authors.forename: Jaivinder
authors.initials: J
authors.lastname: Yadav
authors.forename: Vandana
authors.initials: V
authors.lastname: Jain
authors.forename: Rajesh
authors.initials: R
authors.lastname: Khadgawat
authors.forename: Mahuya
authors.initials: M
authors.lastname: Sikdar
authors.forename: Ayurchelvan
authors.initials: A
authors.lastname: Bhavatharini
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Das
authors.forename: Tanvir
authors.initials: T
authors.lastname: Kaur
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Radha
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002096:C-Peptide / Q000097:blood; D044903:Congenital Hyperinsulinism / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D003981:Diazoxide; D006801:Humans; D007194:India / Q000453:epidemiology; D007328:Insulin / Q000097:blood; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017422:Sequence Analysis, DNA; D064233:Sulfonylurea Receptors / Q000235:genetics*
chemical_list: C577507:ABCC8 protein, human; D002096:C-Peptide; D007328:Insulin; D064233:Sulfonylurea Receptors; D003981:Diazoxide
keywords: ABCC8 gene; GLUD1 gene; KCNJ11 gene; hyperinsulinemia