GATA6基因变异致胰腺发育不全1例并文献复习  

Pancreatic agenesis caused by GATA6 gene mutation: a case report and literature review

作　　者：林梅[1] 成淑淇 朱晓波[1] 薛江[1] 宋薇[3] 梁爽[3] 张雪[1] Mei Lin;Shuqi Cheng;Xiaobo Zhu;Jiang Xue;Wei Song;Shuang Liang;Xue Zhang(Department of Neonatology,the Second Hospital of Shandong University,Jinan 250033,China;Department of Pediatrics,the Second Clinical College of Shandong University,Jinan 250033,China;Department of Children's Medical Center,the Second Hospital of Shandong University,Jinan 250033,China)

机构地区：[1]山东大学第二医院新生儿科,济南250033 [2]山东大学第二临床学院儿科,济南250033 [3]山东大学第二医院儿童医学中心,济南250033

出　　处：《中华新生儿科杂志（中英文）》2023年第12期721-726,共6页Chinese Journal of Neonatology

基　　金：山东省自然科学基金青年项目(ZR2020QH059)。

摘　　要：目的探讨GATA6基因变异致胰腺发育不全患儿的基因型和临床表型特征, 提高临床医生对胰腺发育不全的认识。方法对山东大学第二医院新生儿科收治的1例胰腺发育不全新生儿的临床资料进行回顾性分析。以"胰腺发育不全"、"GATA6"和"pancreatic agenesis/hypoplasia"、"GATA6 transcription factor"为主题词, 对中国知网、万方数据库、维普生物医学数据库、中华医学期刊全文数据库、PubMed、Embase、SCI数据库收录的文献进行检索, 检索时间为建库至2022年10月31日, 总结已报道的GATA6基因变异致胰腺发育不全患者的基因变异特点和临床特征。结果本例患儿为足月男婴, 生后2 d出现依赖胰岛素控制的高血糖、脂肪泻, 并伴有宫内生长受限、先天性心脏病、隐睾。基因检测结果为GATA6基因(c.1366C>T)新发杂合变异, 符合常染色体显性遗传, 患儿及其父母表型和基因型符合共分离, ACMG变异评级为致病变异。静脉输注胰岛素、皮下注射胰岛素或长效胰岛素效果均不佳, 应用门冬胰岛素持续皮下泵入联合口服胰酶替代治疗后好转出院。随访患儿至15月龄, 持续胰岛素皮下泵入控制血糖, 胰腺外分泌功能恢复正常, 生长发育大致正常。检索到22篇文献, 报道59例, 加上本例共60例, 其中先证者47例, 13例为家系成员, 61.7%(29/47)为新发变异。共有39种变异基因型, 错义变异占28.2%(11/39), 无功能变异占71.8%(28/39)。GATA6基因变异可导致广泛的表型谱, 胰腺表型主要包括新生儿糖尿病(39例)、胰腺外分泌功能不全(39例);胰腺外表型包括不同类型的先天性心脏病(54例)、肝胆系统发育异常(23例)、神经系统表型(18例)、消化系统表型(16例)、生殖内分泌系统表型(15例)。结论 GATA6基因杂合变异可导致胰腺发育不全, 并具有广泛的表型谱, 胰腺表型主要为新生儿糖尿病和胰腺外分泌不全, 胰腺外表型有先天性心�Objective To explore the genotype and clinical phenotype characteristics of patients with pancreatic agenesis caused by GATA6 gene mutations and to improve the clinical understanding of pancreatic agenesis.Methods The clinical data of a newborn with pancreatic agenesis admitted to the Second Hospital of Shandong University were retrospectively analyzed.Relevant literature published until October 31,2022,were retrieved from China National Knowledge Infrastructure,Wanfang Database,VIP Database,Chinese Medical Journal Full Text Database,PubMed,Embase and SCI Database with the terms of"pancreatic agenesis","GATA6","pancreatic agenesis/hypoplasia"and"GATA6 Translation Factor".The characteristics of gene variants and clinical manifestations of patients diagnosed with pancreatic agenesis caused by GATA6 gene mutation were retrieved and summarized.Results This case was a full-term male infant who developed insulin dependent hyperglycemia and fatty diarrhea 2 d after birth,accompanied by intrauterine growth restriction,congenital heart disease,and cryptorchidism.Genetic testing showed a novel heterozygous mutation of GATA6(c.1366C>T)which was consistent with the autosomal dominant inheritance pattern.The phenotype and genotype between the proband and his parents were consistent with the cosegregation.The ACMG mutation was rated as pathogenic variant.Intravenous infusion of insulin,subcutaneous injection of insulin,or long-acting insulin were not effective.After continuous subcutaneous pumping of aspartic insulin combined with oral pancreatic enzyme replacement therapy,the infant's condition was improved and discharged.Follow up to age of 15 months,the patient still relied on continuously subcutaneous pump to control blood glucose,pancreatic exocrine function was back to normal,and the development was generally normal.A total of 59 cases were reported in 22 articles,with the case from our hospital,there were 60 patients in total.Among them,47 were probands and 13 were family members,about 61.7%(29/47)of which were de novo

关 键 词：胰腺发育不全 GATA6基因 新生儿糖尿病 胰腺外分泌不足 先天性心脏病 

分 类 号：R722.1[医药卫生—儿科]