Flanagan Sarah E, Patch Ann-Marie, Mackay Deborah J G, Edghill Emma L, Gloyn Anna L, Robinson David, Shield Julian P H, Temple Karen, Ellard Sian, Hattersley Andrew T
Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK.
Diabetes. 2007 Jul;56(7):1930-7. doi: 10.2337/db07-0043. Epub 2007 Apr 19.
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 with ATP-sensitive K+ channel (K(ATP) channel) gene mutations have been reported. We determined the 6q24 status in 97 patients with TNDM. In patients in whom no abnormality was identified, the KCNJ11 gene and/or ABCC8 gene, which encode the Kir6.2 and SUR1 subunits of the pancreatic beta-cell K(ATP) channel, were sequenced. K(ATP) channel mutations were found in 25 of 97 (26%) TNDM probands (12 KCNJ11 and 13 ABCC8), while 69 of 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 who were diagnosed and remitted earlier (all P < 0.001). K(ATP) channel mutations were identified in 26 additional family members, 17 of whom had diabetes. Of 42 diabetic patients, 91% diagnosed before 6 months remitted, but those diagnosed after 6 months had permanent diabetes (P < 0.0001). K(ATP) channel mutations account for 89% of patients with non-6q24 TNDM and result in a discrete clinical subtype that includes biphasic diabetes that can be treated with sulfonylureas. Remitting neonatal diabetes was observed in two of three mutation carriers, and permanent diabetes occurred after 6 months of age in subjects without an initial diagnosis of neonatal diabetes.
短暂性新生儿糖尿病（TNDM）在出生后的前6个月被诊断出来，在婴儿期或幼儿期缓解。大约50%的患者糖尿病会在以后的生活中复发。大多数病例是由6号染色体q24印记区域的异常引起的，并且已经报道了14例患有ATP敏感性钾通道（K(ATP)通道）基因突变的患者。我们确定了97例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K(ATP)通道的Kir6.2和SUR1亚基的KCNJ11基因和/或ABCC8基因进行了测序。在97例TNDM先证者中有25例（26%）发现了K(ATP)通道突变（12例KCNJ11和13例ABCC8），而97例中有69例（71%）存在6号染色体q24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患者明显不同（所有P<0.001）。在另外26名家庭成员中发现了K(ATP)通道突变，其中17人患有糖尿病。在42例糖尿病患者中，6个月前诊断的患者91%缓解，但6个月后诊断的患者患有永久性糖尿病（P<0.0001）。K(ATP)通道突变占非q24 TNDM患者的89%，并导致一种离散的临床亚型，包括可用磺脲类药物治疗的双相性糖尿病。在三名突变携带者中有两名观察到缓解性新生儿糖尿病，在最初未诊断为新生儿糖尿病的受试者中，6个月龄后出现永久性糖尿病。
