Dominant form of congenital hyperinsulinism maps to HK1 region on 10q.
Dominant form of congenital hyperinsulinism maps to HK1 region on 10q.
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DOI：
10.1159/000351943
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发表时间：
2013
影响因子：
3.2
通讯作者：
Stanley CA
中科院分区：
文献类型：
--
作者：
Pinney SE;Ganapathy K;Bradfield J;Stokes D;Sasson A;Mackiewicz K;Boodhansingh K;Hughes N;Becker S;Givler S;Macmullen C;Monos D;Ganguly A;Hakonarson H;Stanley CA
在MacQuarrie于20世纪50年代首次描述的一个先天性高胰岛素血症（HI）家族中，我们研究了一种新型显性HI的遗传位点和临床表型。我们调查了25名受影响的个体，其中7人参加了胰岛素失调测试（24小时空腹，口服葡萄糖和蛋白质耐量测试）。为了鉴定疾病位点和潜在的疾病相关突变，我们进行了连锁分析、全转录组测序、全基因组测序、基因捕获和下一代测序。大多数患者在一岁之前被诊断为HI，40%的患者表现为癫痫发作。所有患者对二氮嗪反应良好。受影响者在口服葡萄糖耐量试验或长时间禁食后不能充分抑制胰岛素分泌;无蛋白敏感性低血糖。连锁分析将HI定位在含有48个基因的Chr 10 q21 -22区域。在己糖激酶1（HK 1）中发现了三种新的非编码变体，在DNA 2的编码区发现了一种错义变体。在这个家族中占主导地位的二氮嗪反应性HI映射到Chr 10 q21 -22上的一个新位点。HK 1是更有吸引力的疾病候选基因，因为干扰β细胞中HK 1表达正常抑制的突变可以容易地解释该家系的低血糖表型。
In a family with congenital hyperinsulinism (HI), first described in the 1950s by MacQuarrie, we examined the genetic locus and clinical phenotype of a novel form of dominant HI. We surveyed 25 affected individuals, 7 of whom participated in tests of insulin dysregulation (24-hour fasting, oral glucose and protein tolerance tests). To identify the disease locus and potential disease-associated mutations we performed linkage analysis, whole transcriptome sequencing, whole genome sequencing, gene capture, and next generation sequencing. Most affecteds were diagnosed with HI before age one and 40% presented with a seizure. All affecteds responded well to diazoxide. Affecteds failed to adequately suppress insulin secretion following oral glucose tolerance test or prolonged fasting; none had protein-sensitive hypoglycemia. Linkage analysis mapped the HI locus to Chr10q21–22, a region containing 48 genes. Three novel non-coding variants were found in hexokinase 1 (HK1) and one missense variant in the coding region of DNA2. Dominant, diazoxide-responsive HI in this family maps to a novel locus on Chr10q21–22. HK1 is the more attractive disease gene candidate since a mutation interfering with the normal suppression of HK1 expression in beta-cells could readily explain the hypoglycemia phenotype of this pedigree.
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影响因子：
7.7
作者：
Henquin JC;Sempoux C;Marchandise J;Godecharles S;Guiot Y;Nenquin M;Rahier J
通讯作者：
Rahier J
影响因子：
7.7
作者：
Bonnefond A;Vaxillaire M;Labrune Y;Lecoeur C;Chèvre JC;Bouatia-Naji N;Cauchi S;Balkau B;Marre M;Tichet J;Riveline JP;Hadjadj S;Gallois Y;Czernichow S;Hercberg S;Kaakinen M;Wiesner S;Charpentier G;Lévy-Marchal C;Elliott P;Jarvelin MR;Horber F;Dina C;Pedersen O;Sladek R;Meyre D;Froguel P
通讯作者：
Froguel P
影响因子：
56.9
作者：
KATO, H;HORIKOSHI, M;ROEDER, RG
通讯作者：
ROEDER, RG
影响因子：
5.4
作者：
Coull, JJ;Romerio, F;Margolis, DM
通讯作者：
Margolis, DM
影响因子：
56.9
作者：
Grimsby, J;Sarabu, R;Grippo, JF
通讯作者：
Grippo, JF