Analysis of a case with gonadal mosaicism for COL1A2 variant.
10.3760/cma.j.issn.1003-9406.2020.05.007
- VernacularTitle:COL1A2基因生殖腺嵌合变异的分析
- Author:
Haiyan ZHU
1
;
Yuanyuan CHEN
;
Lili WANG
;
Weizhou WANG
;
Sheng HE
Author Information
1. Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, the Sixth Medical Center of PLA General Hospital, Beijing 100048, China. fbird2004@sina.com.
- Publication Type:Case Reports
- MeSH:
Adult;
Child;
Collagen Type I;
genetics;
Female;
Fetus;
Gonadal Disorders;
genetics;
Humans;
Male;
Mosaicism;
Mutation;
Osteogenesis Imperfecta;
diagnosis;
genetics;
Pregnancy;
Prenatal Diagnosis;
Whole Exome Sequencing
- From:
Chinese Journal of Medical Genetics
2020;37(5):523-526
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic basis for a couple with normal phenotype but repeated pregnancies with fetuses affected by osteogenesis imperfecta.
METHODS:Whole exome sequencing (WES) was carried out on fetal specimens and parental DNA to detect potential pathologic variants. Suspected variants were verified by Sanger sequencing. Semen sample of the husband was collected for the extraction of genome DNA, and whole genome amplification (WGA) was performed for single sperms isolated from the sample.
RESULTS:WES has identified a heterozygous c.1378G>A (p.G460S) variant of the COL1A2 gene in the fetus, which was predicted to be pathogenic but not detected in peripheral blood samples of both husband and wife. The heterozygotic variant was detected in semen DNA from the husband. Among 15 spermatozoa, 4 were found to harbor the variant.
CONCLUSION:The fetus was diagnosed with osteogenesis imperfecta, and the gonadal mosaicism probably accounted for the repeated abnormal pregnancies. Possibility of gonadal mosaicism should be considered when counseling couples with normal phenotype and genotype but recurrent abnormal pregnancies and/or births of children with similar phenotypes and genetic variants.
