Abstract Title

IRF6 gene Variants in Etiology of Nonsyndromic Cleft Lip and Palate, and in Syndromes with Orofacial Clefts

Lead Author Affiliation

Doctor of Dental Surgery/Department of Orthodontics

Lead Author Status

DDS Year 2

Expected Graduation Date

2020

Presentation Category

Research

Introduction/Context/Diagnosis

Craniofacial development of embryo and fetus is one of the most delicate processes of human prenatal development and is most prone to errors resulting in facial congenital malformations. Tightly regulated cascades of transcription factors and signaling factors control this process. Changes in DNA sequence of transcription factor and signaling molecule genes involved in craniofacial development can lead to a plethora of congenital anomalies in the head and facial regions. Our gene of interest is interferon regulatory factor 6 (IRF6). Mutations of this gene are correlated with abnormalities of the face, skin and genitalia. Our objective is to review literature in order to determine if a mutation of the IRF6 gene is involved in etiology of non-syndromic cleft lip with or without palate (NSCL/P), as it is involved in the autosomal-dominant Van der Woude Syndrome (VWS) and Popliteal Pterygium Syndrome (PPS).

Methods/Treatment Plan

Four search engines (PubMed, Scorpius, Google Scholar, and Science Direct) were used to collect research articles, systematic reviews, and meta-analyses on craniofacial development, IRF6, and IRF6 mutations and variants.

Results/Outcome

While the search provided a large number of articles, 16 most relevant articles were selected to summarize. IRF6 protein has two highly conserved domains, a DNA-binding and a protein-binding domain. IRF6 mutations in the DNA-binding domain can lead to disorders such as PPS and mutations in either DNA- or protein-binding domain can lead to VWS. The structural genetic basis of the IRF6 link leading to NSCL/P has been extensively studied, but has not been identified yet.

Significance/Conclusions

Current research aiming to find etiological relationships between specific loci and NSCL/P has fallen short and a list of genetic contenders has gotten longer. Etiology of NSCL/P is complex and includes genetic factors interacting with environmental factors, such as nutrients and folic acid. VWS served as a study model for NSCL/P since about 15% of affected individuals had isolated CL/P, while the majority had only additional minor phenotypes. Identification of the genetic and environmental basis of NSCL/P will move us closer to a reliable diagnosis as well as prevention methods for this prevalent serious condition.

Comments/Acknowledgements

Keywords: craniofacial development, IRF6, and IRF6 mutations and variants.

Format

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IRF6 gene Variants in Etiology of Nonsyndromic Cleft Lip and Palate, and in Syndromes with Orofacial Clefts

Craniofacial development of embryo and fetus is one of the most delicate processes of human prenatal development and is most prone to errors resulting in facial congenital malformations. Tightly regulated cascades of transcription factors and signaling factors control this process. Changes in DNA sequence of transcription factor and signaling molecule genes involved in craniofacial development can lead to a plethora of congenital anomalies in the head and facial regions. Our gene of interest is interferon regulatory factor 6 (IRF6). Mutations of this gene are correlated with abnormalities of the face, skin and genitalia. Our objective is to review literature in order to determine if a mutation of the IRF6 gene is involved in etiology of non-syndromic cleft lip with or without palate (NSCL/P), as it is involved in the autosomal-dominant Van der Woude Syndrome (VWS) and Popliteal Pterygium Syndrome (PPS).