2例MED13L综合征患者临床表型和基因变异分析  

Clinical phenotype and genetic analysis of two cases with MED13L syndrome

作　　者：梁喆[1] 刘月芳 LIANG Zhe;LIU Yuefang(Genetics Department of Huai’an Maternal and Child Health Care Hospital,Huai’an,Jiangsu 223002,China)

机构地区：[1]淮安市妇幼保健院医学遗传与产前诊断科,江苏淮安223002

出　　处：《中国优生与遗传杂志》2024年第9期1896-1900,共5页Chinese Journal of Birth Health & Heredity

基　　金：淮安市自然科学研究基金项目(HAB202217)。

摘　　要：病例1为2月龄男孩,出生时低体重、缺氧窒息、四肢肌张力低、复苏后精神反应差、颅骨形态异常和脑电图异常。病例2为1岁女孩,其母孕期宫内发育迟缓、双侧侧脑室扩大及脑部透明隔异常。出生后发育迟缓、肌张力低下、智力低下、特殊面容(扁平鼻梁、满月脸和张嘴)。全外显子组测序发现病例1携带MED13L c.3519_3530delCTACAATTCAGG(p.Tyr1174_Gly1177del)氨基酸缺失变异,病例2携带MED13L c.2605C>A(p.Pro869Thr)错义变异,均为新发的未报道过的变异,按照美国医学遗传学与基因组学学会指南均判读为可能致病。后期随访均显示语言运动全面发育落后。MED13L突变类型为主要功能丧失性变异,偶见错义变异,尚未见单个氨基酸缺失变异,病例1突变类型为首次报道。查询文献发现已报道3名患者携带病例2相同位置不同氨基酸的Pro869Ser变异,因此证明Pro869为变异热点。Case 1 was a 2-month-old boy who was born with low weight,hypoxic asphyxia,hypotonia,poor mental response after resuscitation,abnormal skull morphology,and abnormal electroencephalogram.Case 2 was a 1-year-old girl who was diagnosed as intrauterine growth restriction,bilateral lateral ventricular enlargement,and abnormal septum pellucida during pregnancy.After birth,delayed development,hypotonia,mental retardation and facial deformities(flat nose bridge,moon face,and open mouth)were observed.Whole exome sequencing(WES)showed that both cases carried the de novo MED13L variants,with c.3519_3530delCTACAATTCAGG(p.Tyr1174_Gly1177del)in case 1 and c.2605C>A(p.Pro869Thr)in case 2.Both variants have not been reported and were evaluated as likely pathogenic according to the American College of Medical Genetics and Genomics(ACMG).Follow-up results showed that both two cases had intellectual disability,delayed language and motor development.The MED13L mutation type is characterized by the main loss-of-function variant and occasional missense variants.Single amino acid deletion variant has not been reported so far.The mutation type in case 1 is reported for the first time.Three patients with MED13L Pro869Ser variants have been reported,in addition to case 2 with MED13L Pro869Thr variant,thus proving that Pro869 was a hotspot variant.

关 键 词：MED13L综合征 MED13L变异 氨基酸缺失 错义变异 

分 类 号：R725.9[医药卫生—儿科]