A clinical and multi-omics study of Van der Woude syndrome in three generations of a Chinese family
| Autor: | Jue Wu, Jian‑Jiang Zhu, Li Lin, You‑Sheng Yan, Ya Tan, Dong‑Liang Zhang, Kai Yang, Xing‑Yue Dong |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male interferon regulatory factor 6 China Cancer Research Cleft Lip Mutation Missense Context (language use) Biology Biochemistry Exon Genetics medicine Humans Missense mutation Abnormalities Multiple Van der Woude syndrome whole-exome sequencing Family history Child Medical History Taking Molecular Biology Gene Anodontia cleft palate Family Characteristics Polymorphism Genetic Cysts Infant whole-transcriptome sequencing Exons Articles Middle Aged medicine.disease Lip Pedigree Hypodontia Phenotype Oncology Child Preschool Interferon Regulatory Factors Molecular Medicine Female IRF6 Transcriptome |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Previous studies have suggested that pathogenic variants in interferon regulatoryse factor 6 (IRF6) can account for almost 70% of familial Van der Woude Syndrome (VWS) cases. However, gene modifiers that account for the phenotypic variability of IRF6 in the context of VWS remain poorly characterized. The aim of this study was to report a family with VWS with variable expressivity and to identify the genetic cause. A 4‑month‑old boy initially presented with cleft palate and bilateral lower lip pits. Examination of his family history identified similar, albeit milder, clinical features in another four family members, including bilateral lower lip pits and/or hypodontia. Peripheral blood samples of eight members in this three‑generation family were subsequently collected, and whole‑exome sequencing was performed to detect pathogenic variants. A heterozygous missense IRF6 variant with a c.1198C>T change in exon 9 (resulting in an R400W change at the amino acid level) was detected in five affected subjects, but not in the other three unaffected subjects. Moreover, subsequent structural analysis was indicative of damaged stability to the structure in the mutant IRF protein. Whole‑transcriptome sequencing, expression analysis and Gene Ontology enrichment analysis were conducted on two groups of patients with phenotypic diversity from the same family. These analyses identified significant differentially expressed genes and enriched pathways in these two groups. Altogether, these findings provide insight into the mechanism underlying the variable expressivity of VWS. |
| Databáze: | OpenAIRE |
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