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Novel Mutations in the IRF6 Gene on the Background of Known Polymorphisms in Polish Patients With Orofacial Clefting.
Cleft Palate Craniofac J. 2015 09; 52(5):e161-7.CP

Abstract

OBJECTIVE

To examine the role of the IRF6 mutations in Polish families with Van der Woude syndrome and popliteal pterygium syndrome and to determine the effect of IRF6 single nucleotide polymorphisms (rs7552506, rs2013162, and rs2235375) on cleft lip and/or palate susceptibility.

DESIGN

IRF6 mutation screening was performed by direct sequencing of all coding exons of the gene and their flanking intronic regions. Cosegregation analysis was performed to establish the relation of single nucleotide polymorphisms and cleft lip and/or palate phenotypes.

PATIENTS

We screened the IRF6 gene in eight families with clinical recognition of Van der Woude syndrome and popliteal pterygium syndrome.

RESULTS

In five families we identified pathogenic mutations, all affecting the DNA-binding or the protein-binding domain of IRF6. Two of the mutations were novel-a missense mutation Arg31Thr and a small deletion Trp40Glyfs*23. In most cases we found also a haplotype of three single nucleotide polymorphisms-rs7552506, rs2013162, and rs2235375. The association of the single nucleotide polymorphisms and cleft lip and/or palate susceptibility has been previously published. The variants did not cosegregate with phenotype in examined families nor did they cosegregate with pathogenic mutations. The single nucleotide polymorphisms were deemed not causative, due to their presence in unaffected family members.

CONCLUSIONS

Two novel mutations (Arg31Thr and Trp40Glyfs*23) in the IRF6 gene were identified to be causative for Van der Woude and popliteal pterygium syndromes. In the present study no association between the single nucleotide polymorphisms rs7552506, rs2013162, and rs2235375 and the cleft lip and/or palate phenotype was found. The hypothesis, whether the haplotype of the three single nucleotide polymorphisms was correlated with IRF6 expression level, demands further investigation.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25489771

Citation

Charzewska, Agnieszka, et al. "Novel Mutations in the IRF6 Gene On the Background of Known Polymorphisms in Polish Patients With Orofacial Clefting." The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association, vol. 52, no. 5, 2015, pp. e161-7.
Charzewska A, Obersztyn E, Hoffman-Zacharska D, et al. Novel Mutations in the IRF6 Gene on the Background of Known Polymorphisms in Polish Patients With Orofacial Clefting. Cleft Palate Craniofac J. 2015;52(5):e161-7.
Charzewska, A., Obersztyn, E., Hoffman-Zacharska, D., Lenart, J., Poznański, J., & Bal, J. (2015). Novel Mutations in the IRF6 Gene on the Background of Known Polymorphisms in Polish Patients With Orofacial Clefting. The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association, 52(5), e161-7. https://doi.org/10.1597/14-030
Charzewska A, et al. Novel Mutations in the IRF6 Gene On the Background of Known Polymorphisms in Polish Patients With Orofacial Clefting. Cleft Palate Craniofac J. 2015;52(5):e161-7. PubMed PMID: 25489771.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel Mutations in the IRF6 Gene on the Background of Known Polymorphisms in Polish Patients With Orofacial Clefting. AU - Charzewska,Agnieszka, AU - Obersztyn,Ewa, AU - Hoffman-Zacharska,Dorota, AU - Lenart,Jacek, AU - Poznański,Jarosław, AU - Bal,Jerzy, Y1 - 2014/12/09/ PY - 2014/12/10/entrez PY - 2014/12/10/pubmed PY - 2014/12/10/medline KW - IRF6 KW - IRF6 polymorphisms KW - cleft lip and palate SP - e161 EP - 7 JF - The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association JO - Cleft Palate Craniofac J VL - 52 IS - 5 N2 - OBJECTIVE: To examine the role of the IRF6 mutations in Polish families with Van der Woude syndrome and popliteal pterygium syndrome and to determine the effect of IRF6 single nucleotide polymorphisms (rs7552506, rs2013162, and rs2235375) on cleft lip and/or palate susceptibility. DESIGN: IRF6 mutation screening was performed by direct sequencing of all coding exons of the gene and their flanking intronic regions. Cosegregation analysis was performed to establish the relation of single nucleotide polymorphisms and cleft lip and/or palate phenotypes. PATIENTS: We screened the IRF6 gene in eight families with clinical recognition of Van der Woude syndrome and popliteal pterygium syndrome. RESULTS: In five families we identified pathogenic mutations, all affecting the DNA-binding or the protein-binding domain of IRF6. Two of the mutations were novel-a missense mutation Arg31Thr and a small deletion Trp40Glyfs*23. In most cases we found also a haplotype of three single nucleotide polymorphisms-rs7552506, rs2013162, and rs2235375. The association of the single nucleotide polymorphisms and cleft lip and/or palate susceptibility has been previously published. The variants did not cosegregate with phenotype in examined families nor did they cosegregate with pathogenic mutations. The single nucleotide polymorphisms were deemed not causative, due to their presence in unaffected family members. CONCLUSIONS: Two novel mutations (Arg31Thr and Trp40Glyfs*23) in the IRF6 gene were identified to be causative for Van der Woude and popliteal pterygium syndromes. In the present study no association between the single nucleotide polymorphisms rs7552506, rs2013162, and rs2235375 and the cleft lip and/or palate phenotype was found. The hypothesis, whether the haplotype of the three single nucleotide polymorphisms was correlated with IRF6 expression level, demands further investigation. SN - 1545-1569 UR - https://www.unboundmedicine.com/medline/citation/25489771/Novel_Mutations_in_the_IRF6_Gene_on_the_Background_of_Known_Polymorphisms_in_Polish_Patients_With_Orofacial_Clefting_ L2 - https://journals.sagepub.com/doi/10.1597/14-030?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -