Identification of a novel heterozygous missense mutation of SEMA3E (c.1327G>A; p. Ala443Thr) in a labor induced fetus with CHARGE syndrome

BACKGROUND: CHARGE syndrome is a complex multisystem genetic disease. We aimed to find the potential gene mutation in the labor induced fetus with CHARGE syndrome. METHODS: Genomic DNA was extracted from the fetal thigh muscle tissue and the peripheral blood of his parents. The resulting exomes were sequenced using whole exome sequencing (WES) followed by the selection of the candidate causative mutation genes. The deleteriousness of the identified variants was predicted. Analysis of multiple alignment of protein sequences and protein conserved domains was performed by online software. Finally, Sanger sequencing was applied for validation of the identified variants in the WES. RESULTS: After sequencing and bioinformatics filtering, a heterozygous missense mutation of SEMA3E (c.1327G>A; p. Ala443Thr) was found in the fetus, while the mutation was absent in his parents. Genotyping results showed that the mutation cosegregated fully with definite CHARGE phenotypes between the fetus and his parents. This change was located in the Sema superfamily and highly conserved across different species. Sanger validation result was consistent with the WES analysis. CONCLUSION: Our investigations suggested that the heterozygous missense mutation of SEMA3E (c.1327G>A; p. Ala443Thr) may be a potential causal variant in the fetus with CHARGE syndrome.