SBDS基因变异致Shwachman-Diamond综合征1例患儿的临床及遗传学分析  

Genetic and clinical analysis of a child with Shwachman-Diamond syndrome due to compound heterozygous variants of SBDS gene

作　　者：李素丽[1] 于志丹 周方 王欢[1] 王跃生 梅世月 李小芹 Li Suli;Yu Zhidan;Zhou Fang;Wang Huan;Wang Yuesheng;Mei Shiyue;Li Xiaoqin(Department of Gastroenterology,Children's Hospital Affiliated to Zhengzhou University,Henan Children's Hospital,Zhengzhou Children's Hospital,Zhengzhou,Henan 450018,China;Henan Provincial Engineering Research Center of Childhood Neurodevelopment,Zhengzhou,Henan 450018,China)

机构地区：[1]郑州大学附属儿童医院河南省儿童医院郑州儿童医院消化科,郑州450018 [2]河南省儿童神经发育工程研究中心,郑州450018

出　　处：《中华医学遗传学杂志》2024年第2期209-214,共6页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81903330、81701125);河南省医学科技攻关联合共建项目(LHGJ20220733)。

摘　　要：目的探讨1例SBDS基因变异致Shwachman-Diamond综合征(SDS)患儿的临床特点及基因变异情况。方法选择2022年2月因"间断腹泻、便血7月余"就诊于郑州大学附属儿童医院消化科1例SDS女性患儿作为研究对象,收集其临床资料。收集患儿、患儿父母及其姐姐的外周血样,进行全外显子组测序,并进行Sanger测序验证。结果患儿为1岁1月龄女性,主要表现为腹泻、便血、生长发育迟缓、营养不良,血液转氨酶升高,中性粒细胞和血红蛋白降低。左手腕部正位X射线摄片显示骨龄明显落后。肠镜检查发现结直肠黏膜糜烂,肠腔内可见较多油性食物残渣附着。基因测序显示患儿SBDS基因存在父源c.258+2T>C和母源c.100A>G复合杂合变异。c.258+2T>C为已报道致病性变异。根据美国医学遗传学与基因组学学会变异评级指南,c.100A>G变异评级为可能致病性变异(PM1+PM2Supporting+PM3+PM5+PP3)。结论c.258+2T>C和c.100A>G复合杂合变异考虑是该SDS患儿致病原因。对于难治性腹泻、肝损害和生长迟缓的患儿,需警惕SDS,基因检测有利于明确诊断及指导治疗。Objective To analyze the clinical features and genetic characteristics of a patient with Shwachman-Diamond syndrome(SDS)due to compound heterozygous variants of SBDS gene.Methods A female child with SDS who was admitted to the Children's Hospital Affiliated to Zhengzhou University in February 2022 was selected as the study subject.Clinical data of the child was collected.Peripheral blood samples of the child and her elder sister and parents were collected and subjected to whole exome sequencing(WES).Candidate variant was verified by Sanger sequencing.Results The child,a 1-year-and-1-month-old girl,had mainly manifested with diarrhea,hematochezia,growth retardation and malnutrition,along with increased transaminases and decreased neutrophils and hemoglobin.The anteroposterior X-ray of her left wrist indicated significantly delayed bone age.Colonoscopy revealed that her colorectal mucosa was erosive with oily food residues attached to the intestinal lumen.Genetic testing revealed that she has harbored c.258+2T>C and c.100A>G compound heterozygous variants of the SBDS gene.The c.258+2T>C variant has derived from her father and known to be pathogenic,whilst the other has derived from her mother.Based on the guidelines from the American College of Medical Genetics and Genomics,the c.100A>G variant was classified as likely pathogenic(PM1+PM2_Supporting+PM3+PM5+PP3).Conclusion The compound heterozygous variants of c.258+2T>C and c.100A>G probably underlay the SDS in this child.For children with refractory diarrhea,liver damage and growth retardation,SDS should be suspected,and genetic testing can facilitate the diagnosis and treatment.

关 键 词：SBDS基因 Shwachman-Diamond综合征 基因 变异 儿童 

分 类 号：R725.9[医药卫生—儿科]