全外显子组测序在9p缺失综合征诊断中的应用

doi:10.3969/j.issn.1673-8640.2022.06.008

检验医学 ›› 2022, Vol. 37 ›› Issue (6): 539-542.DOI: 10.3969/j.issn.1673-8640.2022.06.008

全外显子组测序在9p缺失综合征诊断中的应用

易薇¹, 番云华¹, 刘厚昌¹, 禹崇飞¹, 杨必清¹, 葛世军¹, 林克勤², 褚嘉祐², 杨昭庆²()

1.云南省德宏州人民医院检验科,云南芒市 678400
2.中国医学科学院北京协和医学院医学生物学研究所医学遗传学研究室,云南昆明 650118

收稿日期:2020-12-01 修回日期:2022-03-23 出版日期:2022-06-30 发布日期:2022-07-28
通讯作者: 杨昭庆
作者简介:杨昭庆,E-mail： zyang@imbcams.com.cn。
易薇,女,1987年生,硕士,主管检验师,主要从事细胞遗传学相关检测工作。
基金资助:
国家重点研发计划项目(2016YFC1201704);云南省高层次卫生健康技术人才培养专项(L-2018003)

Application of whole exome sequencing in 9p deletion syndrome

YI Wei¹, PAN Yunhua¹, LIU Houchang¹, YU Chongfei¹, YANG Biqing¹, GE Shijun¹, LIN Keqin², CHU Jiayou², YANG Zhaoqing²()

1. Department of Clinical Laboratory,the People's Hospital of Yunnan Province Dehong Prefecture,Mangshi 678400,Yunnan,China
2. Department of Medical Genetics,Institute of Medical Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Kunming 650118,Yunnan,China

Received:2020-12-01 Revised:2022-03-23 Online:2022-06-30 Published:2022-07-28
Contact: YANG Zhaoqing

摘要/Abstract

摘要：

目的探讨1例具有子宫发育不全而无面容异常和智力语言障碍的XX核型女性9p缺失综合征患者的临床及分子细胞遗传学特征。方法对患者及其父母行外周血染色体G显带核型分析,并对患者行全外显子组测序,分析9p末端缺失相关的临床表现、分子细胞遗传学特征及两者之间可能的关联性。结果该例9p末端缺失女性患者的临床症状主要为原发性闭经、幼稚子宫、性激素异常、癫痫等,未见三角头畸形和智力语言障碍等常见的9p缺失综合征典型症状。核型分析结果为46,XX,del（9）（p23）,其父母核型未见异常。全外显子组测序结果显示,患者在9p24.3-p23（24 846~13 022 661）区域存在单拷贝缺失,缺失片段长度约为13.0 Mb,覆盖了61个已知基因,包括DMRT1、DMRT3、DMRT2、DOCK8、KANK1、FOXD4等多个与9p缺失综合征表型密切相关的关键基因,在染色体其他区域并未发现其他致病性拷贝数变异（CNV）、碱基插入和缺失。结论 9p末端缺失导致DMRT1基因单倍剂量不足可能是患者幼稚子宫、原发性闭经的主要致病因素。全外显子组测序提供了与临床表型相关的基因型背景数据。

关键词: 9p缺失综合征, XX核型, 全外显子组测序, 原发性闭经

Abstract:

Objective To report the clinical and molecular cytogenetic characteristics of a XX female patient with 9p deletion syndrome. Methods Chromosome G-banding karyotyping was performed on the patient and her parents,and whole exome sequencing was performed on the patient. The clinical,molecular cytogenetic characteristics and distal deletions on chromosome 9p were analyzed. Results The patient presented with primary amenorrhea,infantile uterus,abnormal level of sex hormones and epilepsy,but without typical clinical features of 9p deletion syndrome such as trigonocephaly and mental retardation. Karyotyping analysis of the patient showed 46,XX,del（9）（p23）,and her parents' karyotypes were normal. Whole exome sequencing showed the patient had a deletion on 9p24.3-p23（24 846-13 022 661,13.0 Mb）,which included critical genes such as DMRT1,DMRT3,DMRT2,DOCK8,KANK1,FOXD4（totally 61 genes）. No other pathogenic copy number variation（CNV）,base insertion and deletion were detected in other regions of chromosomes. Conclusions Haploinsufficiency of one or more genes on the terminal of chromosome 9p may underlie the disorders of sexual development of the patient. Whole exome sequencing provides genotypic data relevant to the clinical phenotypes.

Key words: 9P deletion syndrome, XX karyotype, Whole exome sequencing, Primary amenorrhea

中图分类号:

R446.1

易薇, 番云华, 刘厚昌, 禹崇飞, 杨必清, 葛世军, 林克勤, 褚嘉祐, 杨昭庆. 全外显子组测序在9p缺失综合征诊断中的应用[J]. 检验医学, 2022, 37(6): 539-542.

YI Wei, PAN Yunhua, LIU Houchang, YU Chongfei, YANG Biqing, GE Shijun, LIN Keqin, CHU Jiayou, YANG Zhaoqing. Application of whole exome sequencing in 9p deletion syndrome[J]. Laboratory Medicine, 2022, 37(6): 539-542.

图/表 2

参考文献 15

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全外显子组测序在9p缺失综合征诊断中的应用

Application of whole exome sequencing in 9p deletion syndrome

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