Genetics is the major component of cleft lip and palate susceptibility. Despite efforts to understand this condition, there is much more that needs to be learned. One line of investigation is to consider clefting as only a part of a broader phenotype. This proposal will focus on Dental development to sub-phenotype the common multifactor cleft lip and palate. We posit that tooth agenesis and/or other Dental anomalies could be clinical markers for the risk of having a child with isolated cleft lip and palate. We will focus on a population from the Philippines to take advantage of preliminary data collection already available. In this project, the Specific Aims include: 1) clinical characterization of multifactorial cleft lip and palate through cleft lip and palate case ascertainment along with complete Dental exam; 2) genetics studies of cleft lip and palate by a combination of candidate gene association/TDT and linkage approaches, and; 3) studies of gene-gene and gene-environment interactions. Complete Dental exams will be performed in 154 families from the Philippines with two or more affected siblings. Dental anomalies will be included as an extended phenotype of clefts. These Filipino families already possess substantial molecular information for a number of candidate genes and loci. Also, 392 STRP markers across the genome were typed on these families by The Center for Inherited Disease Research (CIDR) and a genome wide search for cleft loci was performed. Control families will be collected for a complementary case-control approach. We will compare the genetic analyses performed with and without Dental information to identify clefting sub-phenotypes. If our hypothesis is confirmed, we will be able to offer a very powerful tool for advancing etiologic studies of cleft lip and palate and will improve genetic counseling. Dental exams could be applied as screening tool for modifying population risks for cleft lip and palate.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DE016718-01
Application #
6905039
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Mcinnes, Pamela M
Project Start
2005-06-01
Project End
2005-09-23
Budget Start
2005-06-01
Budget End
2005-09-23
Support Year
1
Fiscal Year
2005
Total Cost
$100,375
Indirect Cost
Name
University of Iowa
Department
Pediatrics
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Letra, Ariadne; Fakhouri, Walid; Fonseca, Renata F et al. (2012) Interaction between IRF6 and TGFA genes contribute to the risk of nonsyndromic cleft lip/palate. PLoS One 7:e45441
Letra, Ariadne; Menezes, Renato; Cooper, Margaret E et al. (2011) CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate. Cleft Palate Craniofac J 48:363-70
Küchler, Erika Calvano; da Motta, Luise Gomes; Vieira, Alexandre Rezende et al. (2011) Side of dental anomalies and taurodontism as potential clinical markers for cleft subphenotypes. Cleft Palate Craniofac J 48:103-8
Letra, A; Menezes, R; Fonseca, R F et al. (2010) Novel cleft susceptibility genes in chromosome 6q. J Dent Res 89:927-32
Letra, Ariadne; Menezes, Renato; Govil, Manika et al. (2010) Follow-up association studies of chromosome region 9q and nonsyndromic cleft lip/palate. Am J Med Genet A 152A:1701-10
Letra, Ariadne; Menezes, Renato; Granjeiro, Jose M et al. (2009) AXIN2 and CDH1 polymorphisms, tooth agenesis, and oral clefts. Birth Defects Res A Clin Mol Teratol 85:169-73
Menezes, Renato; Marazita, Mary Louise; Goldstein McHenry, Toby et al. (2009) AXIS inhibition protein 2, orofacial clefts and a family history of cancer. J Am Dent Assoc 140:80-4
Vieira, Alexandre R; McHenry, Toby G; Daack-Hirsch, Sandra et al. (2008) A genome wide linkage scan for cleft lip and palate and dental anomalies. Am J Med Genet A 146A:1406-13
Menezes, Renato; Letra, Ariadne; Ruff, Joe et al. (2008) Studies of genes in the FGF signaling pathway and oral clefts with or without dental anomalies. Am J Med Genet A 146A:1614-7
Menezes, Renato; Vieira, Alexandre Rezende (2008) Dental anomalies as part of the cleft spectrum. Cleft Palate Craniofac J 45:414-9

Showing the most recent 10 out of 15 publications