Xu Aijing, Cheng Jing, Sheng Huiying, Wen Zhe, Lin Yunting, Zhou Zhihong, Zeng Chunhua, Shao Yongxian, Li Cuiling, Liu Li, Li Xiuzhen
Guangzhou Women and Children’s Medical Center, Clinic of Genetics and Endocrinology, Guangzhou, China
Contributed equally to this work
J Clin Res Pediatr Endocrinol. 2019 Nov 22;11(4):400-409. doi: 10.4274/jcrpe.galenos.2019.2019.0046. Epub 2019 Jun 18.
To explore the clinical presentation and molecular genetic characteristics of a cohort of congenital hyperinsulinism (CHI) patients from southern China and also to explore the most appropriate therapeutic approaches.
We retrospectively reviewed a cohort of 65 children with CHI. Mutational analysis was performed for and genes. The gene was sequenced in patients with hyperammonaemia. gene sequencing was performed in those patients with no mutation identified in the or genes.
mutations were identified in 16 (25%) of the cohort, mutations were identified in five children, and no or mutations were identified. Moreover, some unique features of gene mutations in southern Chinese CHI patients were found in this study. The most common mutation was a deletion/insertion mutation p.Thr1042GlnfsX75 was found in five unrelated patients, which possibly represents a relatively common mutation in southern China. Five novel mutations were detected. The mutations were p.Phe5SerfsX72, p.Gln273ArgfsX85, p.Leu724del, p.Asp1447Gly and IVS 25-1G>T. Five compound heterozygous mutations of gene were identified in this study, and three of these patients were diazoxide-responsive. Forty patients were diazoxide-responsive, 13 patients were diazoxide-unresponsive and 12 patients received dietary treatment only. A pancreatectomy was performed in 10 patients who were unresponsive to medical treatment.
To the best of our knowledge, this is the first study of CHI in south China. Mutations in are the most common causes of CHI in this cohort. Diazoxide and dietary treatment were effective in most patients. Multicentre studies are necessary to obtain the long-term follow-up characteristics of such patients at a national level.
探讨中国南方一组先天性高胰岛素血症（CHI）患者的临床表现和分子遗传学特征，并探索最合适的治疗方法。
我们回顾性分析了一组65例CHI患儿。对ABCC8和KCNJ11基因进行突变分析。对高氨血症患者进行谷氨酸脱氢酶（GDH）基因测序。对ABCC8或KCNJ11基因未发现突变的患者进行葡萄糖激酶（GCK）基因测序。
该队列中有16例（25%）患者检测到ABCC8基因突变，5例患儿检测到KCNJ11基因突变，未检测到GDH或GCK基因突变。此外，本研究发现了中国南方CHI患者ABCC8基因突变的一些独特特征。最常见的突变是在5例无血缘关系的患者中发现的缺失/插入突变p.Thr1042GlnfsX75，这可能代表中国南方相对常见的突变。检测到5个新的ABCC8基因突变。这些突变分别为p.Phe5SerfsX72、p.Gln273ArgfsX85、p.Leu724del、p.Asp1447Gly和IVS 25-1G>T。本研究鉴定出5例ABCC8基因复合杂合突变，其中3例患者对二氮嗪有反应。40例患者对二氮嗪有反应，13例患者对二氮嗪无反应，12例患者仅接受饮食治疗。10例药物治疗无效的患者接受了胰腺切除术。
据我们所知，这是中国南方首次对CHI进行的研究。ABCC8基因突变是该队列中CHI最常见的病因。二氮嗪和饮食治疗对大多数患者有效。有必要进行多中心研究以在国家层面获得此类患者的长期随访特征。
