Study of genetic etiology in fetuses with severely short limbs in the first and second trimester using whole exome sequencing
10.3760/cma.j.issn.0529-567x.2019.04.002
- VernacularTitle:全外显子组测序技术用于妊娠早中期严重肢体短小胎儿的病因分析
- Author:
Xinyue ZHANG
1
;
Yanqin YOU
;
Honghui ZHOU
;
Shujuan WANG
;
Xiaoxiao XIE
;
Manli ZHANG
;
Longxia WANG
;
Yanping LU
Author Information
1. 解放军总医院妇产科
- Keywords:
Bone diseases,developmental;
Pregnancy trimester,first;
Pregnancy trimester,second;
Whole exome sequencing;
DNA copy number variations
- From:
Chinese Journal of Obstetrics and Gynecology
2019;54(4):221-225
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate pathogenic genes related to the phenotype of fetus with severely short limbs in the first and second trimester by whole exome sequencing (WES). Methods Thirteen fetuses with severely short limbs detected by ultrasonography in the first and second trimester admitted in Chinese PLA General Hospital from September 2016 to June 2018 were collected. All cases were performed induced abortion, 6 of which were carried out karyotype analysis of amniotic fluid at the same time. WES and copy number variations (CNV) were performed on specimens from fetal tissues after labor induction. The suspected pathogenic mutations were validated by Sanger sequencing reactions. Results No abnormal karyotypes or pathological CNV were found. In 10 fetuses, pathogenic or possibly pathogenic mutations were detected in the following genes: COL2A1, FGFR3, COL1A1, COL1A2, DYNC2LI1 and TRIP11, all of which were essential to skeletal development. The diagnostic yield of WES in the fetuses with severe short limbs was 10/13. Conclusions In the first and second trimester, most of the fetuses with extremely short limbs suffer from monogenic diseases. WES is likely to be a valuable diagnostic testing option for the fetuses with severe short limbs.
