Genetic analysis of two families with Short-rib thoracic dysplasia type 3.
10.3760/cma.j.cn511374-20210205-00115
- VernacularTitle:短肋胸廓发育不良3型两个家系的遗传学分析
- Author:
Xin GUAN
1
;
Huan MI
;
Shan LI
;
Yixuan CAO
;
Jingsong GAO
;
Xiaohui ZHU
;
Xiuli ZHAO
Author Information
1. Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Medical Genetics, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. xiulizhao@ibms.pumc.edu.cn.
- Publication Type:Journal Article
- MeSH:
Humans;
Fetus;
Chloroform;
Computational Biology;
Ethnicity;
Ribs
- From:
Chinese Journal of Medical Genetics
2023;40(11):1350-1355
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the pathogenic variants and clinical classification of two fetuses with Short-rib thoracic dysplasia with or without polydactyly (SRTD).
METHODS:With informed consent obtained, the phenotypic characteristics of the fetuses were comprehensively examined, and genomic DNA was extracted from fetal skin tissue and peripheral blood samples of the parents with conventional phenol-chloroform method. Whole exome sequencing (WES) was carried out on both fetuses, and the candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was analyzed using bioinformatic software VarCards, and the impact of the variants on the protein structure was predicted with Swiss-Pdb-viewer.
RESULTS:Both fetuses were found to harbor compound heterozygous variants of the DYNC2H1 gene, including c.515C>A (p.Pro172Gln) and c.5983G>A (p.Ala1995Thr) in fetus 1, and c.5920G>T (pGly1974) and c.9908T>C (p.He3303Thr) in fetus 2. The parents of both fetuses were heterozygous carriers.
CONCLUSION:The compound heterozygous variants of the DYNC2H1 gene probably underlay the SRTD3 in the two fetuses.
