亮氨酸拉链样转录调节因子1基因复合杂合变异致Noonan综合征家系的产前诊断及文献回顾  

Noonan syndrome in a pedigree caused by compound heterozygous mutations in leucine zipper-like transcription regulator 1 gene:prenatal diagnosis and literature review

作　　者：唐丽君[1] 刘思平[1] 刘慧冰 吴瑞枫[1] 许育双 陈伟珊 贾蓓[1] Tang Lijun;Liu Siping;Liu Huibing;Wu Ruifeng;Xu Yushuang;Chen Weishan;Jia Bei(Center of Prenatal and Hereditary Disease Diagnosis,Department of Obstetrics and Gynecology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]南方医科大学南方医院妇产科产前诊断与遗传病诊断中心,广州510515

出　　处：《中华围产医学杂志》2023年第9期746-753,共8页Chinese Journal of Perinatal Medicine

基　　金：广东省重点领域研发计划(2019B020227001);南方医科大学南方医院院长基金(2020B015)。

摘　　要：目的总结亮氨酸拉链样转录调节因子1(leucine zipper like transcription regulator 1,LZTR1)基因变异所致Noonan综合征(Noonan syndrome,NS)的临床特征及遗传学特点。方法回顾性分析2021年1月因超声提示胎儿颈项透明层(nuchal translucency,NT)增厚及有不良孕产史来南方医科大学南方医院产前诊断中心行介入性产前诊断,家系全外显子测序(whole exome sequencing,WES)确诊为NS的家系的临床资料。以“努南综合征”“Noonan综合征”“亮氨酸拉链样转录调节因子1”“Noonan syndrome”及“LZTR1”为关键词,检索PubMed、Web of Science、中华医学期刊全文数据库、中国知网数据库及万方数据知识服务平台自2013年1月至2022年10月收录的文献。总结和分析国内外报道的LZTR1基因变异所致NS病例的临床表现及遗传学特点。对数据资料采用描述性分析。结果(1)病例资料:该家系WES并经Sanger测序验证发现家系先证者(Ⅱ-2)及胎儿(Ⅱ-3)均存在LZTR1基因c.842C>T及c.2248G>A复合杂合变异,分别来自于父母。结合出生后先证者存在NS典型的特殊面容及身材矮小表型,诊断胎儿及先证者为常染色体隐性遗传NS患儿。孕妇因胎儿全身严重水肿,于妊娠22周终止妊娠。先证者就诊时3岁,存在NS典型的颅面部特征及身材矮小,后于外院儿科进行定期随访,应用重组人生长激素改善身高。4岁上幼儿园,可与小朋友正常交流及游戏。(2)文献回顾:检索并纳入95例LZTR1变异相关NS病例,合并本例胎儿及先证者共97例,涉及79种不同变异位点,呈常染色体隐性遗传43例(44.3%),常染色体显性遗传54例(55.7%)。变异类型以错义变异最常见,无义变异及移码变异多见于复合杂合变异病例中。疾病累及多个器官系统,主要表现为颅面颈部异常、骨骼畸形、先天性心脏病、身材矮小,可合并发育迟缓、学习困难及智力障碍等。描述产前表型的病例18例(18.6%),其中16例Objective To analyze and summarize the clinical and genetic features of Noonan syndrome(NS)caused by mutations in the leucine zipper-like transcription regulator 1(LZTR1)gene.Methods The retrospective study analyzed a patient who was examined at the Center of Prenatal and Hereditary Disease Diagnosis,Department of Obstetrics and Gynecology,Nanfang Hospital,Southern Medical University in January 2021 because of fetal nuchal translucency thickening and a previous history of problematic pregnancies.Subsequently,the patient was diagnosed with Noonan syndrome(NS)through whole exome sequencing.Using keywords such as"Noonan syndrome,""Leucine zipper-like transcription regulator 1",and"LZTR1",clinical and genetic characteristics of NS derived from LZTR1 mutations were summarized by extracting relevant literature from China National Knowledge Infrastructure,Wanfang Database,Yiigle,PubMed and Web of Science,covering from January 2013 to October 2022.Descriptive analysis was applied to the data.Results(1)Case report:WES and Sanger sequencing showed the existence of the biallelic variants of LZTR1 gene c.842C>T and c.2248G>A in the fetus(Ⅱ-3)and the proband(Ⅱ-2)that inherited from the father and the mother,respectively.Based on the typical special facial appearance and short stature in the proband indicative of NS,the fetus and the proband were diagnosed with autosomal recessive inheritance(AR)NS.The pregnant woman terminated her pregnancy at 22 weeks due to severe edema of the fetus.At the age of three,the proband exhibited typical craniofacial features and short stature characteristics of NS when presented to our hospital.The proband received regular follow-ups in the pediatrics department of other hospitals,where recombinant human growth hormone was used to improve his height.He attended kindergarten at age four and can communicate and play with other children normally.(2)Literature review:95 cases of NS associated with LZTR1 mutations have been retrieved and included.When including the fetus and the proband of this c

关 键 词：努南综合征 转录因子 杂合子 遗传变异 产前诊断 回顾性研究 

分 类 号：R714.5[医药卫生—妇产科学]