Prenatal diagnosis of a case with Congenital myasthenic syndrome due to compound heterozygous variants of SCN4A gene
10.3760/cma.j.cn511374-20230316-00139
- VernacularTitle:SCN4A基因复合杂合变异导致先天性肌无力综合征1例
- Author:
Fanrong MENG
1
;
Yunfang SHI
;
Duan JU
;
Xiuyan WANG
;
Haiwei DONG
;
Xuebing LI
;
Xiaozhou LI
;
Xuexia ZHOU
Author Information
1. 天津医科大学总医院妇产科 天津市女性生殖健康与优生重点实验室，天津 300052
- Keywords:
Myasthenic Syndromes, Congenital;
SCN4A gene;
Nav1.4;
Loss-of-function variant
- From:
Chinese Journal of Medical Genetics
2024;41(4):450-455
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical and genetic characteristics of a fetus diagnosed with Congenital myasthenic syndrome type 16 (CMS16).Methods:A couple who had visited Tianjin Medical University General Hospital in February 2018 due to "adverse outcome of two pregnancies" was selected as the study subject. Clinical data was gathered. Peripheral blood and amniotic fluid samples were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Low-depth whole-genome sequencing was carried out to detect copy number variation (CNV) in the fetus.Results:The couple′s first pregnancy had resulted in a miscarriage at 27 + 5 weeks, when ultrasound had revealed pleural effusion and polyhydramnios in the fetus. Their second pregnancy was terminated at 30 + 5 weeks due to fetal hand malformations, polyhydramnios and pleural fluid. Both couple had denied family history of genetic conditions. For their third pregnancy, no CNV abnormality was detected, whilst a compound heterozygous variants, including a maternally derived c. 3172C>T (p.R1058W) and paternal c. 1431delG (p.K477fs*89) in the SCN4A gene were detected. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 3172C>T (p.R1058W) was predicted as a likely pathogenic variant (PM1+ PM2_supporting+ PP3+ PP4), whilst the c. 1431delG (p.K477fs*89) was predicted as a pathogenic variant (PVS1+ PM2_supporting+ PP4). Conclusion:The c. 3172C>T (p.R1058W) and c. 1431delG (p.K477fs*89) compound heterozygous variants of the SCN4A gene probably underlay the CMS16 in the third fetus.
