摘要
目的探讨2个3-M(Miller-Mukusick-Malvaux)综合征家系的临床特征和遗传学病因。方法选取2022年9月和2023年6月就诊于临沂市人民医院的2个3-M综合征家系为研究对象,应用全外显子测序(whole exome sequencing,WES)对先证者进行基因检测,对候选变异进行Sanger测序和致病性评估,并对2个家系中高危胎儿进行产前诊断。结果家系1先证者孕18周,身材矮小、有异常面容,出生时有先天性髋关节脱位现象;WES检出CUL7基因的复合杂合变异:c.4333C>T(p.R1445*)、c.3291_3294del(p.H1098Cfs*42),分别遗传自父亲和母亲,先证者弟弟携带相同的变异,依据美国医学遗传学和基因组学学会相关指南,2个变异位点均评级为致病性变异;先证者胎儿为c.4333C>T变异位点携带者。家系2先证者表现为身材矮小、特殊面容、脊柱侧弯、翼状肩胛骨、双侧斜指、第五指短等,检测到CUL7基因携带遗传自母亲的c.3823del(p.R1275Vfs*34)和遗传自父亲的c.758del(p.L253Rfs*2)复合杂合变异,经评判,上述变异位点分别为致病性变异和疑似致病性变异;胎儿为c.758del变异位点携带者。结论本研究在2个家系中确诊了3例3-M综合征患者,CUL7基因:c.4333C>T、c.3291_3294del和c.3823del、c.758del分别是家系1和家系2的遗传学病因,进一步扩展了CUL7基因变异谱,为遗传咨询和产前诊断提供了依据。
Objective To explore the clinical features and genetic etiology of two Chinese pedigrees affected with 3-M(Miller-Mukusick-Malvaux)syndrome.Methods Two Chinese pedigrees with 3-M syndrome admitted to Linyi People's Hospital in September 2022 and June 2023 were selected as the research objects.Clinical data of the family members was collected,and the peripheral blood was selected for whole exome sequencing(WES)after informed consent.Candidate variants were verified by Sanger sequencing and pathogenicity assessment was conducted.Prenatal diagnosis was performed for high-risk fetuses in two pedigrees.Results The proband of pedigree 1 was 18-weeks pregnant with short stature,abnormal face and congenital dislocation of the hip at birth.WES detected compound heterozygous variants of CUL7 gene:c.4333C>T(p.R1445*),c.3291_3294del(p.H1098Cfs*42),inherited from the father and mother,respectively.The younger brother of the proband carried the same variants.According to the American Society for Medical Genetics and Genomics(ACMG)guidelines,both c.4333C>T and c.3291_3294del were judged to be pathogenic variants.The fetus carried the c.4333C>T variant.The proband from pedigree 2 showed short height,special face,scoliosis,pterygous scapular bone,bilateral oblique finger,short fifth finger,etc.The proband was found to harbor c.3823del(p.R1275Vfs*34)and c.758del(p.L253Rfs*2)compound heterozygous variants of CUL7 gene,which inherited from mother and father,respectively.And they were judged to be pathogenic variants and suspected pathogenic variants.Maternal prenatal diagnosis indicated that the fetus carried the c.758 del variant.Conclusion In this study,three patients with 3-M syndrome were diagnosed in two pedigrees.Two compound heterozygous variants of CUL7 gene were probably the genetic causes of pedigree 1 and pedigree 2,respectively.Above findings expanded the variation spectrum of CUL7 gene in 3-M syndrome and provided a basis for genetic counseling and prenatal diagnosis.
作者
彭海英
刘爱玲
季相妹
王言言
何印龙
高春海
马育华
李琳
PENG Haiying;LIU Ailing;JI Xiangmei;WANG Yanyan;HE Yinlong;GAO Chunhai;MA Yuhua;LI lin(Department of Laboratory Medicine,Linyi PeoplesHospital,Linyi 276000,Shandong,China;Key Laboratory for Laboratory Medicine of Linyi City,Linyi 276000,Shandong,China;Shandong Provincial Medicine and Health Key Laboratory for Precise Diagnosis of Hereditary Rare Diseases,Linyi PeoplesHospital,Linyi 276000,Shandong,China Published:2024-05-16)
出处
《山东大学学报（医学版）》
CAS
北大核心
2024年第4期85-91,共7页
Journal of Shandong University:Health Sciences
基金
山东省重点研发计划(2017GSF218072)
山东省自然科学基金(ZR2021QH104)
山东省医药卫生科技发展计划(202102070553)。
