Genetic analysis of a fetus with Meckel syndrome due to variants of TMEM67 gene
10.3760/cma.j.cn511374-20230201-00045
- VernacularTitle:TMEM67基因变异所致Meckel综合征1例胎儿的遗传学分析
- Author:
Hui TANG
1
;
Xiaoyan SONG
;
Xin WENG
;
Minjuan LIU
;
Nannan ZHAO
Author Information
1. 南京医科大学附属苏州医院，苏州市立医院生殖与遗传中心，苏州 215002
- Keywords:
Meckel syndrome;
TMEM67 gene;
Whole exome sequencing
- From:
Chinese Journal of Medical Genetics
2024;41(2):221-224
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To carry out prenatal diagnosis for a fetus with Meckel syndrome(MKS) and explore its genetic basis.Methods:A pregnant woman presented at Suzhou Municipal Hospital in February 2018 was selected as the study subject. Clinical data was collected. Muscle tissue sample from the abortus and peripheral blood samples from the couple were collected. Genomic DNA was extracted and subjected to chromosomal microarray analysis (CMA) and whole exome sequencing. Candidate variant was verified by Sanger sequencing.Results:The fetus was found to have microcephaly, oligohydramnios, polycystic kidneys and banana-shaped cerebellum at 18 weeks of gestation. After induction of labor, it was found to have encephalocele, renal cysts and polydactyly. CMA has found no abnormality. Whole exome sequencing revealed novel compound heterozygous variants c. 296delA (p.Lys99SerfsTer6) and c. 1243G>A (p.Val415Met) in the TMEM67 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 296delA variant was predicted to be pathogenic (PVS1+ PM2_Supporting+ PP4), whilst the c. 1243G>A variant was predicted to be likely pathogenic (PM2_Supporting+ PM3+ PP3_Moderate+ PP4). Conclusion:The c. 296delA and c. 1243G>A compound heterozygous variants of the TMEM67 gene probably underlay the MKS in this fetus.
