A Novel IRF6 Frameshift Mutation in a Large Chinese Pedigree With Van der Woude syndrome.
Cleft Palate Craniofac J
; 59(4): 548-553, 2022 Apr.
Article
em En
| MEDLINE
| ID: mdl-33906476
ABSTRACT
AIMS:
Van der Woude syndrome (VWS) is one of the most common craniofacial anomalies, causing significant functional and psychological burden to the patients. This study aimed to identify the genetic cause of VWS in a Chinese family.METHODS:
Whole genome sequencing (WGS) was performed to screen for pathogenic mutations. Various Bioinformatics tools were used to assess the pathogenicity of the variants. Cosegregation analysis of the candidate variant was carried out. Interpretation of variants was performed according to the American College of Medical Genetics and Genomics guidelines.RESULTS:
A novel frameshift duplication c.373_374dupAA (p.Asn125Lys fs*43) was identified in exon 4 of the interferon regulatory factor 6 (IRF6) gene in all 3 affected members, which were not found in unaffected family members. The novel mutation leads to a frameshift and a premature stop codon which caused putative truncated protein. Protein alignment indicated high evolutionary conservation of the p.N125 residue, and this mutation was predicted by online tools to be damaging and deleterious.CONCLUSIONS:
This study demonstrates that the novel mutation c.373_374dupAA (p.Asn125Lysfs*43) in the IRF6 gene corresponds to the VWS in this family. The discovery of this pathogenic variant enriches the genotypic spectrum of IRF6 gene and contributes to genetic diagnosis and counseling of families with VWS.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mutação da Fase de Leitura
/
Fenda Labial
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Fissura Palatina
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Fatores Reguladores de Interferon
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article