Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India.
Clin Genet. 2013 May;83(5):439-45. doi: 10.1111/j.1399-0004.2012.01939.x. Epub 2012 Aug 20.
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.
胰腺 ATP 敏感性钾（K+）通道蛋白（磺酰脲受体 1[SUR1]和内向整流钾[K+]通道 Kir6.2[Kir6.2]）的突变是新生儿糖尿病的最常见原因。我们描述了患有新生儿糖尿病和单基因糖尿病综合征的亚洲印度儿童的临床表现和分子特征。我们对 33 名发病年龄在 1 岁以下的印度无关先证者的 KCNJ11、ABCC8 和胰岛素（INS）基因进行了测序。共发现 12 种突变，包括 7 种 ABCC8 突变、3 种 KCNJ11 突变和 2 种 INS 突变。ABCC8 中的 Asp212Tyr 突变是新发现的。我们还在有综合征形式糖尿病的儿童中检测到两种新突变（Val67Met 和 Leu19Arg），如 Berardinelli-Seip 综合征[1-酰基-sn-甘油-3-磷酸酰基转移酶β（AGPAT2）]和 Fanconi-Bickel 综合征[溶质载体家族 2A2（SLC2A2）]。携带 KCNJ11（Cys42Arg，Arg201Cys）和 ABCC8（Val86Ala，Asp212Tyr）突变的儿童已成功从胰岛素治疗转为口服磺脲类药物。我们的研究是印度首例大规模新生儿糖尿病基因筛查研究。
