Zhang Jin, Wang Jiyang, Chen Hui
Gansu Women's and Children's Hospital, Lanzhou, China.
Institute of Systems Engineering, Macao University of Science and Technology, Macao, China.
Front Pediatr. 2022 Aug 11;10:914267. doi: 10.3389/fped.2022.914267. eCollection 2022.
Congenital hyperinsulinemia (CHI) is an inherited disease of abnormal insulin secretion and is the main cause of persistent and intractable hypoglycemia in infants. The aim of this case report was to investigate the genetic mechanisms and treatment of CHI in an affected patient.
We collected clinical data from, and performed gene capture, high-throughput gene sequencing analysis, and Sanger sequencing validation, in a child with CHI and his family to identify the causative gene mutations. Two heterozygous pathogenic mutations in the ATP-binding cassette subfamily C member 8 () gene were detected in the child: c.863G>A (p.Trp288Ter) in exon 6 and c.2506C>T (p.Arg836Ter) in exon 21. Sanger sequencing showed that c.863G>A was inherited from heterozygous mutations in the paternal line and c.2506C>T from heterozygous mutations in the maternal line.
The child was a CHI with a biallelic recessive heterozygous mutations in ABCC8 resulting in impairment of its encoded ATP-sensitive potassium (KATP) channel, poor response to diazoxide treatment, and developed diabetes after subtotal pancreatectomy.
先天性高胰岛素血症（CHI）是一种胰岛素分泌异常的遗传性疾病，是婴儿持续性和顽固性低血糖的主要原因。本病例报告的目的是研究一名患病患者CHI的遗传机制及治疗方法。
我们收集了一名CHI患儿及其家族的临床资料，并对其进行基因捕获、高通量基因测序分析和桑格测序验证，以鉴定致病基因突变。在该患儿中检测到ATP结合盒亚家族C成员8（ABCC8）基因的两个杂合致病性突变：外显子6中的c.863G>A（p.Trp288Ter）和外显子21中的c.2506C>T（p.Arg836Ter）。桑格测序显示，c.863G>A遗传自父系杂合突变，c.2506C>T遗传自母系杂合突变。
该患儿为ABCC8双等位基因隐性杂合突变导致的CHI，其编码的ATP敏感性钾（KATP）通道受损，对二氮嗪治疗反应不佳，全胰切除术后发生糖尿病。
