title: Clinical and molecular characterization of neonatal diabetes and monogenic syndromic diabetes in Asian Indian children.
abstract: Mutations in the pancreatic ATP sensitive K(+) channel proteins [sulfonyluea receptor 1 (SUR1) and inward rectifier K(+) channel Kir6.2 (Kir6.2), encoded by ATP-binding cassette transporter subfamily C member 8 (ABCC8) and potassium channel J11 (KCNJ11), respectively], are the most common cause of neonatal diabetes. We describe the clinical presentation and molecular characterization of Asian Indian children with neonatal diabetes mellitus and monogenic syndromes of diabetes. We sequenced KCNJ11, ABCC8 and insulin (INS) genes in 33 unrelated Indian probands with onset of diabetes below one year of age. A total of 12 mutations were identified which included ABCC8 mutations in seven, KCNJ11 mutations in three and INS mutations in two children. The Asp212Tyr mutation in ABCC8 was novel. We also detected two novel mutations (Val67Met and Leu19Arg) in children with syndromic forms of diabetes like Berardinelli Seip syndrome [1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2)] and Fanconi Bickel syndrome [solute carrier family 2A2 (SLC2A2)]. Children carrying the KCNJ11 (Cys42Arg, Arg201Cys) and ABCC8 (Val86Ala, Asp212Tyr) mutations have been successfully switched over from insulin therapy to oral sulfonylurea. Our study is the first large genetic screening study of neonatal diabetes in India.
authors: Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India.
authors: S
authors: S
authors: Jahnavi
authors: V
authors: V
authors: Poovazhagi
authors: V
authors: V
authors: Mohan
authors: D
authors: D
authors: Bodhini
authors: P
authors: P
authors: Raghupathy
authors: A
authors: A
authors: Amutha
authors: P
authors: P
authors: Suresh Kumar
authors: P
authors: P
authors: Adhikari
authors: M
authors: M
authors: Shriraam
authors: T
authors: T
authors: Kaur
authors: A K
authors: AK
authors: Das
authors: J
authors: J
authors: Molnes
authors: P R
authors: PR
authors: Njolstad
authors: R
authors: R
authors: Unnikrishnan
authors: V
authors: V
authors: Radha
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D017668:Age of Onset; D002648:Child; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007194:India; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human