A clinical and multiomics study of Van der Woude syndrome in three generations of a Chinese family.
Mol Med Rep
; 22(4): 2925-2931, 2020 Oct.
Article
em En
| MEDLINE
| ID: mdl-32945398
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 4monthold 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 threegeneration family were subsequently collected, and wholeexome 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. Wholetranscriptome 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
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Anormalidades Múltiplas
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Características da Família
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Fenda Labial
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Fissura Palatina
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Mutação de Sentido Incorreto
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Cistos
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Fatores Reguladores de Interferon
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Lábio
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2020
Tipo de documento:
Article