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浙江大学学报（医学版）
浙江大学学报（医学版）  2020, Vol. 49 Issue (5): 581-585    DOI: 10.3785/j.issn.1008-9292.2020.10.05
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淋巴水肿-双行睫综合征一家系遗传学及临床表型分析
胡刚1,2(),刘蓓1,陈敏1,钱叶青1,董旻岳1,*()
1. 浙江大学医学院附属妇产科医院生殖遗传科 生殖遗传教育部重点实验室, 浙江 杭州 310006
2. 湖州市妇幼保健院妇产科, 浙江 湖州 313000
Genetic analysis and clinical phenotype of a family with lymphedema-distichiasis syndrome
HU Gang1,2(),LIU Bei1,CHEN Min1,QIAN Yeqing1,DONG Minyue1,*()
1. Department of Reproductive Genetics, Women's Hospital, Zhejiang University School of Medicine, Key Laboratory of Reproductive Genetics, Ministry of Education, Hangzhou 310006, China
2. Department of Gynecology and Obstetrics, Huzhou Maternity & Child Health Care Hospital, Huzhou 313000, Zhejiang Province, China
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摘要：

目的: 探讨一个淋巴水肿-双行睫综合征家系的遗传学原因。方法: 提取先证者（胎儿流产物）DNA行全外显子组测序，初步确定候选致病基因。收集先证者父母及其他家系共8位成员的外周血，通过PCR扩增及Sanger测序等行基因突变检测，并分析其与表型的相关性。结果: 先证者、母亲、外婆、舅舅、外舅公临床表现为双行睫或下肢静脉曲张，均存在FOXC2：c.595dupC杂合移码突变，其他无临床表型的受检者不存在该突变。结论: FOXC2基因c.595dupC杂合突变是该家系的遗传学病因，可导致常染色体显性遗传淋巴水肿-双行睫综合征，孕期表现为胎儿颈部透明带增厚、胎儿水肿，存在自愈可能。
关键词： 遗传性疾病, 先天性;  常染色体显性;  淋巴水肿-双行睫综合征;  颈部透明度;  胎儿水肿;  全外显子组测序    
Abstract:

Objective: To identify the genetic causes of a family with lymphedema-distichiasis syndrome (LDS). Methods: The whole exome sequencing was performed in a aborted fetus as the proband, and a candidate gene was identified. Peripheral blood of 8 family members were collected. Genotypic-phenotypic analysis were carried out through PCR amplification and Sanger sequencing. Results: The proband, and the mother, grandmother, uncle, granduncle of the proband all had distichiasis or varix of lower limb carried a FOXC2:c.595dupC frame shift mutation, and other subjects without any significant phenotypes did not present the mutation. Conclusion: The FOXC2:c.595dupC frame shift mutation is the genetic cause of this family, which can lead to autosomal dominantly LDS, presenting nuchal translucency thickening and hydrops fetal during pregnancy, and the prognosis is usually good.
Key words: Genetic diseases, inborn    Autosomal dominant    Lymphedema-distichiasis syndrome    Nuchal translucency    Hydrops fetalis    Whole exome sequencing
收稿日期: 2020-07-02 出版日期: 2020-11-19
:  R394.3  
基金资助: 浙江省重点研发计划(2019C03025)
通讯作者: 董旻岳     E-mail: ibmxii@163.com;dongmy@zju.edu.cn
作者简介: 胡刚(1979-), 男, 硕士研究生, 主治医师, 主要从事妇产科临床工作; E-mail:ibmxii@163.com; https://orcid.org/0000-0002-0103-2907
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引用本文:

胡刚,刘蓓,陈敏,钱叶青,董旻岳. 淋巴水肿-双行睫综合征一家系遗传学及临床表型分析[J]. 浙江大学学报（医学版）, 2020, 49(5): 581-585.

HU Gang,LIU Bei,CHEN Min,QIAN Yeqing,DONG Minyue. Genetic analysis and clinical phenotype of a family with lymphedema-distichiasis syndrome. J Zhejiang Univ (Med Sci), 2020, 49(5): 581-585.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2020.10.05    或    http://www.zjujournals.com/med/CN/Y2020/V49/I5/581

图 1  一例淋巴水肿-双行睫综合征患者的家系图谱
图 2  一家系FOXC2基因c.595dupC位点Sanger测序结果
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