Analysis of a Chinese pedigree affected with Meckel syndrome due to variants of TMEM67 gene.
10.3760/cma.j.cn511374-20210626-00544
- VernacularTitle:TMEM67基因变异致麦克尔综合征一个家系的遗传学分析
- Author:
Ganye ZHAO
1
;
Xiaoyan ZHAO
;
Xuechao ZHAO
;
Conghui WANG
;
Zhihui JIAO
;
Qianqian LI
;
Xiangdong KONG
Author Information
1. Genetics and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. kongxdgene@163.com.
- Publication Type:Journal Article
- MeSH:
Female;
Pregnancy;
Humans;
Pedigree;
East Asian People;
Ciliary Motility Disorders/genetics*;
Ciliopathies;
Abortion, Spontaneous;
Membrane Proteins/genetics*
- From:
Chinese Journal of Medical Genetics
2023;40(10):1236-1240
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic etiology for a Chinese pedigree affected with Meckel syndrome.
METHODS:A pedigree with a history of three consecutive adverse pregnancies which presented at the First Affiliated Hospital of Zhengzhou University on August 31, 2017 was selected as the study subject. Clinical data of the pedigree were collected. High-throughput sequencing was carried out to screen for variants of ciliopathy-related genes in the third fetus following induced abortion, and candidate variant was verified by Sanger sequencing.
RESULTS:The first pregnancy of the couple had ended as spontaneous abortion, whilst the fetus of the second pregnancy was suspected for having ciliopathy, though no genetic testing was carried out following elected abortion. The fetus of the third pregnancy was suspected for having ciliopathy, and high-throughput sequencing and Sanger sequencing had shown that the fetus had harbored compound heterozygous variants of the TMEM67 gene, including c.978+1G>A from the father and c.1288G>C (p.D430H) from the mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.978+1G>A was classified as a pathogenic variant (PVS1+PM2_Supporting+PP5), whilst the newly discovered c.1288G>C (p.D430H) was classified as a likely pathogenic variant (PM2_Supporting+PM3+PM5+PP3).
CONCLUSION:The c.978+1G>A and c.1288G>C (p.D430H) compound heterozygous variants of the TMEM67 gene probably underlay the three consecutive adverse pregnancies suspected for ciliopathy in this pedigree. The discovery of c.1288G>C (p.D430H) has also expanded the mutational spectrum of the TMEM67 gene.
