Xu Zi-di, Yu He-fen, Sang Yan-mei, Zhang Yao-nan, Yan Jie, Wu Yu-jun, Zhu Cheng, Ni Gui-chen
Capital Medical University, Beijing, China.
Zhonghua Yi Xue Za Zhi. 2013 Apr 9;93(14):1089-92.
To explore the ABCC8, KCNJ11, and GLUD1 gene mutations of the 11 patients diagnosed as congenital hyperinsulinism (CHI).
A total of 11 CHI children hospitalized in Beijing Children's Hospital from November 2008 to February 2012 and their parents were chosen as the study subjects. Direct sequencing of PCR-DNA was used to analyze the 39 exons of ABCC8 gene, non-translational region and exon of KCNJ11 gene and 6, 7, 10, 11 and 12 exons of GLUD1 gene.
An P629PfsX17 heterozygous mutation of ABCC8 gene was detected in case 1 and his father, an W288X heterozygous mutation of ABCC8 gene was detected in case 4 and his father, A640V and Q1196X mutations in ABCC8 gene in case 5 whose father only carried the Q1196X mutation. In case 6 and his father, an R269H mutation was found in GLUD1 gene. The genotype of 4 children's mothers was normal. No mutations were found in other 7 patients and their parents.
The ABCC8 gene mutations are the main pathogenic mechanisms of Chinese children with CHI. In Chinese, P629PfsX17, W288X, A640V and Q1196X heterozygous mutation of ABCC8 gene and R269H heterozygous mutation of GLUD1 gene may lead to CHI. The inheritance mode of the mutations may be paternally or de novo.
探究11例诊断为先天性高胰岛素血症（CHI）患者的ABCC8、KCNJ11和GLUD1基因突变情况。
选取2008年11月至2012年2月在北京儿童医院住院的11例CHI患儿及其父母作为研究对象。采用PCR-DNA直接测序法分析ABCC8基因的39个外显子、KCNJ11基因的非翻译区和外显子以及GLUD1基因的6、7、10、11和12号外显子。
病例1及其父亲检测到ABCC8基因P629PfsX17杂合突变；病例4及其父亲检测到ABCC8基因W288X杂合突变；病例5检测到ABCC8基因A640V和Q1196X突变，其父亲仅携带Q1196X突变。病例6及其父亲检测到GLUD1基因R269H突变。4名患儿母亲的基因型正常。其他7例患者及其父母未发现突变。
ABCC8基因突变是中国CHI患儿的主要致病机制。在中国人群中，ABCC8基因的P629PfsX17、W288X、A640V和Q1196X杂合突变以及GLUD1基因的R269H杂合突变可能导致CHI。这些突变的遗传方式可能为父系遗传或新发突变。
