MYH11延长突变导致巨膀胱-小结肠-肠蠕动不良综合征1例报告及文献复习  

Megacystis-microcolon-intestinal hypoperistalsis syndrome caused by MYH11 elongating mutation:a case report and literatures review

作　　者：周洁 刘克强 王金玲 王莹[1,2,3] ZHOU Jie;LIU Keqiang;WANG Jinling;WANG Ying(Division of Pediatric Gastroenterology and Nutrition,Xinhua Hospital,School of Medicine,Shanghai Jiao Tong University;Shanghai Institute for Pediatric Research;Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院儿消化营养科 [2]上海市儿科医学研究所 [3]上海市小儿消化与营养重点实验室,上海200092

出　　处：《临床儿科杂志》2024年第9期798-804,共7页Journal of Clinical Pediatrics

基　　金：国家自然科学基金资助项目(No.82370525,No.82200599);上海市自然科学基金资助项目(No.22ZR1441100,No.22ZR1451300,No.21YF1437700);上海市“科技创新行动计划”医学创新研究专项项目(No.22Y31900600);上海市“医苑新星”杰出青年医学人才项目(No.2023005);上海市卫生健康委员会卓越项目(No.20234Z0004)。

摘　　要：目的报告1例MYH11基因杂合新发突变导致巨膀胱-小结肠-肠蠕动不良综合征(MMIHS)患儿的临床表现与遗传信息,并通过文献回顾性分析进行基因型-表型关联研究。方法分析2023年10月因“反复腹胀、呕吐3年余”来院就诊的MMIHS患儿临床资料,采集患儿及父母与姐姐的外周血样,通过Trio-WES及Sanger测序筛查致病突变。并对相关文献进行总结分析。结果患儿,男,15岁,主要临床表现为频繁发作的腹胀、呕吐和腹痛,腹部立位片及上消化道造影提示肠梗阻,给予灌肠、抗感染和静脉营养支持等治疗后病情稳定。基因检测结果显示,患儿携带MYH11基因杂合新发变异c.5819delC(p.Pro1940Hisfs*91),该变异导致肌球蛋白重链C端延长,父母及姐姐均未检测出该变异。文献检索共纳入7篇与MYH11基因变异有关文献,变异类型包括错义突变、移码突变和染色体微缺失。共20例,2例因提前终止妊娠性别不明,其余患者男女比2∶1。基因型-表型关联分析发现,15例携带MYH11基因延长突变显性遗传患者的发病年龄9(0~28)岁,尚未报道死亡案例。5例携带双等位基因丧失功能突变的隐性遗传患者发病年龄均小于1岁,死亡4例(80%)。结论本例MMIHS患儿携带MYH11基因c.5819delC(p.Pro1940Hisfs*91)变异。与携带MYH11基因变异隐性遗传的患者相比,MYH11延长突变显性遗传患者大部分发病较晚,临床表现较轻,生存率较高。Objective To report the clinical characteristics and genetic variant of a patient with megacystismicrocolon-intestinal hypoperistalsis syndrome(MMIHS)and to investigate the genotypic-phenotypic correlation through literatures review.Methods The clinical data of a MMIHS child who came to our hospital in October 2023 due to"repeated abdominal distension and vomiting for more than 3 years"were analyzed.Peripheral blood samples were collected from the patient,his parents and his older sister,and the pathogenic mutation was screened by Trio-WES and Sanger sequencing.Relevant literature was summarized and analyzed.Results The patient,a 15-year-old boy,presented with recurrent episodes of abdominal distension,vomiting,and abdominal pain.Abdominal X-ray and upper gastrointestinal contrast study indicated intestinal obstruction.The condition stabilized after treatment with enema,anti-infection and intravenous nutritional support.Genetic testing revealed a heterozygous mutation in the MYH11 gene,identified as c.5819delC(p.Pro1940Hisfs*91),which resulted in the extension of the C-end of the myosin heavy chain and was not detected by either parent or sister.A total of 7 articles related to MYH11 gene mutation were included in the literature review.Mutation types included missense mutations,frameshift mutations,and chromosomal microdeletion.Gender was undetermined in 2 out of 20 patients due to early termination of pregnancy.Among the remaining patients,the male-to-female ratio was 2:1.Genotypic-phenotypic correlation analysis found that 15 patients with dominant heterozygous protein‐elongating MYH11 variants were aged 9(0-28)years at onset,and no deaths were reported.Five patients with recessive loss-of-function mutations had an onset age of less than 1 year,with 4 deaths(80%).Conclusion This MMIHS patient carries the MYH11 gene c.5819 delC(p.Pro 1940 Hisfs*91)mutation.Compared with patients with MYH11 gene mutation recessive inheritance,those with dominant MYH 11 mutations tend to have a later onset,milder clinical manife

关 键 词：巨膀胱-小结肠-肠蠕动不良综合征 MYH11基因 儿童 

分 类 号：R725.7[医药卫生—儿科]