Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene
Abstract Background Craniofacial microsomia (CFM) is a common congenital malformation with unknown pathogenesis. Although few cases have been reported, it is suggested that variants of the SF3B2 gene may lead to CFM. We herein report the case of a neonate with CFM exhibiting rare features of airway...
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.2268 |
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| author | Yongli Zhang Shaohua Bi Liying Dai Yuwei Zhao Yu Liu Zifeng Shi |
| author_facet | Yongli Zhang Shaohua Bi Liying Dai Yuwei Zhao Yu Liu Zifeng Shi |
| author_sort | Yongli Zhang |
| collection | DOAJ |
| description | Abstract Background Craniofacial microsomia (CFM) is a common congenital malformation with unknown pathogenesis. Although few cases have been reported, it is suggested that variants of the SF3B2 gene may lead to CFM. We herein report the case of a neonate with CFM exhibiting rare features of airway obstruction. Methods Trio whole‐exome sequencing and Sanger validation were performed on the proband and her parents. Candidate gene mutations were analyzed using the Genome Aggregation Database (gnomAD) for normal frequency distributions. The Human Splicing Finder (HSF) and Rare Disease Data Center (RDDC) RNA splicer algorithms predicted the variant's harmfulness, verified by a Minigene assay. Results The proband had a heterozygous SF3B2 variant, NM_006842.3:c.777+1G>A. The patient's father also carried this variant and exhibited facial abnormalities. The variant was not in gnomAD, and HSF and RDDC RNA splicers indicated donor site disruption. The minigene assay suggested that two mRNA products were produced, leading to a premature termination codon. Conclusion For this family, the pathogenesis of CFM may have been caused by an SF3B2 splicing variant. Affected family members exhibited varying degrees of malformation, indicating that CFM has phenotypic heterogeneity. This finding expands the phenotype and variant spectrum of SF3B2, enriches neonatal CFM research, and provides a possible guide to genetic counseling. |
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| format | Article |
| id | doaj.art-7a3fe530a6fb4bd989943e236c6a24dd |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-08T22:57:35Z |
| publishDate | 2023-12-01 |
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| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-7a3fe530a6fb4bd989943e236c6a24dd2023-12-16T05:49:02ZengWileyMolecular Genetics & Genomic Medicine2324-92692023-12-011112n/an/a10.1002/mgg3.2268Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 geneYongli Zhang0Shaohua Bi1Liying Dai2Yuwei Zhao3Yu Liu4Zifeng Shi5Department of Neonatology Children’s Hospital of Fudan University at Anhui (Anhui Provincial Children’s Hospital) Hefei Anhui Province ChinaDepartment of Neonatology Children’s Hospital of Fudan University at Anhui (Anhui Provincial Children’s Hospital) Hefei Anhui Province ChinaDepartment of Neonatology Children’s Hospital of Fudan University at Anhui (Anhui Provincial Children’s Hospital) Hefei Anhui Province ChinaDepartment of Neonatology Children’s Hospital of Fudan University at Anhui (Anhui Provincial Children’s Hospital) Hefei Anhui Province ChinaDepartment of Neonatology Children’s Hospital of Fudan University at Anhui (Anhui Provincial Children’s Hospital) Hefei Anhui Province ChinaCenter of Imaging Diagnosis Children’s Hospital of Fudan University at Anhui (Anhui Provincial Children’s Hospital) Hefei Anhui Province ChinaAbstract Background Craniofacial microsomia (CFM) is a common congenital malformation with unknown pathogenesis. Although few cases have been reported, it is suggested that variants of the SF3B2 gene may lead to CFM. We herein report the case of a neonate with CFM exhibiting rare features of airway obstruction. Methods Trio whole‐exome sequencing and Sanger validation were performed on the proband and her parents. Candidate gene mutations were analyzed using the Genome Aggregation Database (gnomAD) for normal frequency distributions. The Human Splicing Finder (HSF) and Rare Disease Data Center (RDDC) RNA splicer algorithms predicted the variant's harmfulness, verified by a Minigene assay. Results The proband had a heterozygous SF3B2 variant, NM_006842.3:c.777+1G>A. The patient's father also carried this variant and exhibited facial abnormalities. The variant was not in gnomAD, and HSF and RDDC RNA splicers indicated donor site disruption. The minigene assay suggested that two mRNA products were produced, leading to a premature termination codon. Conclusion For this family, the pathogenesis of CFM may have been caused by an SF3B2 splicing variant. Affected family members exhibited varying degrees of malformation, indicating that CFM has phenotypic heterogeneity. This finding expands the phenotype and variant spectrum of SF3B2, enriches neonatal CFM research, and provides a possible guide to genetic counseling.https://doi.org/10.1002/mgg3.2268craniofacial microsomiaSF3B2 gene variantswhole‐exome sequencing |
| spellingShingle | Yongli Zhang Shaohua Bi Liying Dai Yuwei Zhao Yu Liu Zifeng Shi Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene Molecular Genetics & Genomic Medicine craniofacial microsomia SF3B2 gene variants whole‐exome sequencing |
| title | Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene |
| title_full | Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene |
| title_fullStr | Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene |
| title_full_unstemmed | Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene |
| title_short | Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene |
| title_sort | clinical report and genetic analysis of a chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene |
| topic | craniofacial microsomia SF3B2 gene variants whole‐exome sequencing |
| url | https://doi.org/10.1002/mgg3.2268 |
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