Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations.
Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations.
复制标题
DOI：
10.1530/eje-14-0852
复制
发表时间：
2015-06
影响因子：
5.8
通讯作者：
Hussain K
中科院分区：
文献类型：
--
作者：
Demirbilek H;Arya VB;Ozbek MN;Houghton JA;Baran RT;Akar M;Tekes S;Tuzun H;Mackay DJ;Flanagan SE;Hattersley AT;Ellard S;Hussain K
新生儿糖尿病(NDM)是一种罕见的单基因糖尿病，通常出现在生命的前6个月。我们的目的是描述来自单一中心的大量土耳其NDM患者的临床特征和分子遗传学，并估计土耳其东南部安纳托利亚地区NDM的年发病率。纳入了2010至2013年间在迪亚巴克尔州立儿童医院就诊的NDM患者，以及在6个月前发病的假定为1型糖尿病的随访患者。进行分子遗传学分析。22名患者(59%男性)被诊断为非糖尿病(TNDM-5；PNDM-17)。分子遗传学分析在20名(95%)接受突变分析的患者中发现了突变。在一过性新生儿糖尿病(TNDM)患者中，染色体6q24异常3例，ABCC8 1例，INS纯合子1例。在永久性新生儿糖尿病(PNDM)患者中，发现GCK(n=6)、EIF2AK3(n=3)、PTF1a(n=3)、INS(n=1)和KCNJ11(n=2)纯合子突变。在PTF1a远端增强子突变的患者中观察到胰腺外分泌功能障碍。两名携带KCNJ11突变的患者对口服磺脲类药物均有反应。在PNDM和TNDM患者中都发现了c.-331C>；A INS纯合子突变，这是一种可变的表型。土耳其安纳托利亚东南部地区的PNDM年发病率为48万分之一的 活产儿。GCK、EIF2AK3和PTF1A远端增强子区纯合子突变是本组NDM最常见的原因。突变的高检测率可能反映了新的基因技术(有针对性的下一代测序)的贡献以及我们队列中血缘关系的增加。
Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey. NDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed. Twenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3), ABCC8 (n=1) and homozygous INS (n=1). In permanent neonatal diabetes (PNDM) patients, homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous KCNJ11 (n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distal PTF1A enhancer. Both patients with a KCNJ11 mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>A INS mutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births. Homozygous mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort.