Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood.
Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood.
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DOI：
10.2337/db07-0043
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发表时间：
2007-07
期刊：
影响因子：
7.7
通讯作者：
Hattersley AT
中科院分区：
文献类型：
--
作者：
Flanagan SE;Patch AM;Mackay DJ;Edghill EL;Gloyn AL;Robinson D;Shield JP;Temple K;Ellard S;Hattersley AT
暂时性新生儿糖尿病 (TNDM) 在生命的前 6 个月内被诊断出来，并在婴儿期或幼儿期得到缓解。大约 50% 的患者的糖尿病会在以后的生活中复发。大多数病例是由染色体 6q24 印记区域异常引起的，据报道有 14 名患者存在 KATP 通道基因突变。我们确定了 97 名 TNDM 患者的 6q24 状态。在未发现异常的患者中，对编码胰腺 β 细胞 ATP 敏感钾 (KATP) 通道的 Kir6.2 和 SUR1 亚基的 KCNJ11 基因和/或 ABCC8 基因进行了测序。 25/97 (26%) TNDM 先证者 (12 KCNJ11, 13 ABCC8) 发现 KATP 通道突变，而 69/97 (71%) 存在染色体 6q24 异常。与 KCNJ11 和 ABCC8 突变相关的表型相似，但与出生体重较低、诊断和缓解较早的 6q24 患者显着不同（均 p <0.001）。在另外 26 名家庭成员中发现了 KATP 通道突变，其中 17 人患有糖尿病。在 42 名糖尿病患者中，91% 在 6 个月前诊断的患者病情缓解，但 6 个月后诊断的患者患有永久性糖尿病 (p<0.0001)。 KATP 通道突变占非 6q24 TNDM 患者的 89%，并导致离散的临床亚型，其中包括可以用磺脲类药物治疗的双相糖尿病。在 2/3 突变携带者中观察到缓解型新生儿糖尿病，而在未初步诊断为新生儿糖尿病的受试者中，6 个月后出现永久性糖尿病。
Transient neonatal diabetes mellitus (TNDM) is diagnosed in the first 6 months of life with remission in infancy or early childhood. For approximately 50% of patients their diabetes will relapse in later life. The majority of cases result from anomalies of the imprinted region on chromosome 6q24 and 14 patients have been reported with KATP channel gene mutations. We determined the 6q24 status in 97 patients with TNDM. In patients where no abnormality was identified the KCNJ11 gene and/or ABCC8 gene which encode the Kir6.2 and SUR1 subunits of the pancreatic beta-cell ATP sensitive potassium (KATP) channel were sequenced. KATP channel mutations were found in 25/97 (26%) TNDM probands (12 KCNJ11, 13 ABCC8) while 69/97 (71%) had chromosome 6q24 abnormalities. The phenotype associated with KCNJ11 and ABCC8 mutations was similar, but markedly different from 6q24 patients who had a lower birth weight, and were diagnosed and remitted earlier (all p <0.001). KATP channel mutations were identified in 26 additional family members, 17 had diabetes. Of the 42 diabetic patients, 91% diagnosed before 6 months remitted, but those diagnosed after 6 months had permanent diabetes (p<0.0001). KATP channel mutations account for 89% of patients with non-6q24 TNDM and result in a discrete clinical subtype which includes biphasic diabetes that can be treated with sulphonylureas. Remitting neonatal diabetes was observed in 2/3 mutation carriers and permanent diabetes occurred after 6 months of age in subjects without an initial diagnosis of neonatal diabetes.
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影响因子：
7.7
作者：
Temple, IK;Gardner, RJ;Shield, JPH
通讯作者：
Shield, JPH
影响因子：
3.5
作者：
Temple, IK;Gardner, RJ;Shield, JPH
通讯作者：
Shield, JPH
影响因子：
3.5
作者：
Proks, Peter;Arnold, Amanda L.;Ellard, Sian
通讯作者：
Ellard, Sian
影响因子：
2.5
作者：
Shields, BM;Knight, B;Hattersley, AT
通讯作者：
Hattersley, AT
影响因子：
5.3
作者：
Mackay, D. J. G.;Boonen, S. E.;Temple, I. K.
通讯作者：
Temple, I. K.