Genetic analysis of 21 fetuses with high suspicion of congenital skeletal malformation by prenatal ultrasound
10.3760/cma.j.cn113903-20210414-00353
- VernacularTitle:21例产前超声高度怀疑先天性骨骼系统畸形胎儿的遗传学分析
- Author:
Ke YANG
1
;
Yuwei ZHANG
;
Guiyu LOU
;
Na QI
;
Bing KANG
;
Hai XIAO
;
Dong WU
;
Yuan GAO
;
Xingxing LEI
;
Fengyang WANG
;
Xiaodong HUO
;
Bing ZHANG
;
Shixiu LIAO
Author Information
1. 郑州大学人民医院 河南省人民医院医学遗传研究所，郑州 450003
- Keywords:
Musculoskeletal abnormalities;
Congenital abnormalities;
Karyotyping;
Microarray analysis;
Whole exome sequencing
- From:
Chinese Journal of Perinatal Medicine
2022;25(1):28-34
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic etiology of fetuses with high suspicion of congenital skeletal malformation detected by prenatal ultrasound.Methods:This retrospective study collected 21 pregnant women with highly suspected fetal skeletal malformation indicated by ultrasound (the couples had no skeletal malformation) at Institute of Medical Genetics, Henan Provincial People's Hospital from January 2019 to August 2020. Amniotic fluid/umbilical cord blood of the fetus and peripheral blood of the couples were obtained for karyotype analysis, chromosomal microarray analysis, and whole-exome sequencing. Sanger sequencing was performed for the "pathogenic" "suspected pathogenic" "variants of uncertain significance" variants detected by whole exome sequencing. Genetic etiology of the 21 fetuses was described.Results:A total of five chromosomal abnormalities were detected, including four cases of trisomy 21 and one trisomy 18. Chromosome microarray analysis detected one case of abnormal copy number variation, 16 p11.2 microdeletion syndrome. Ten cases of monogenic diseases were found by whole exome sequencing and eight genes were involved ( SGMS2, FGFR3, DYNC2H1, WDR35, TBX5, COL2A1, FGFR2, and ALPL). Totally, 14 variations were detected, among which seven were novel variations (c.8129T>A, c.7126G>A, c.10307_10320del, and c.2641G>T in DYNC2H1 gene; c.3085G>A and c.491G>A in WDR35 gene; c.1070G>T in COL2A1 gene). Conclusions:For fetus, whose parents have no skeletal malformation, highly suspected of congenital malformation of skeletal system by prenatal ultrasound, genetic factor is the primary reason, including chromosomal abnormalities, copy number variations, and monogenic mutations.
