The Society of Craniofacial Genetics. Abstracts of the 2010 annual meeting

Abstract

The Society of Craniofacial Genetics, founded in 1975 with the motto:‘‘Educatio, Investigatio, Communicatio’’ held its 33rd annual meeting and symposium at the National Institute of Dental and Craniofacial Research (NIDCR) in Bethesda, MD on the November 2, 2010. The discrepancy between the founding year and the number of annual meetings is the result of 2 years of missed meetings. The Society previously had two publications:‘‘The Locus,’’ a newsletter of the Society and an official journal: Journal of Craniofacial Genetics and Developmental Biology published by Blackwell, that ceased publication in 2000. The establishment of an official website (http://craniofacialgenetics. org) in 2004 allowed for the posting of abstracts presented at the 1998 and all subsequent meetings. The website has attracted over 5000 ‘‘visits’’ from over 25 countries during the past year, and provides an historical record of the past 12 annual meetings. Attached hereunder are some of the abstracts presented at the 2010 meeting. The topics at this meeting ranged from extracellular matrices through the genetics of palatogenesis to proposed therapeutics for cleft palate fusion. The unpublished 2010 abstracts are available on the Society’s website under ‘‘Abstracts.’’ The 34th annual meeting of the Society will be held in conjunction with the 12th International Congress of Human Genetics and the 61st annual meeting of the American Society of Human Genetics in Montreal, Canada in 2011. Common and rare variants in the PAX7 and VAX1 genes contribute to orofacial cleft etiology A. Butali, M.A. Mansilla, S. Suzuki, T.H. Beaty, M.L. Marazita, J.C. Murray Department of Pediatrics, University of Iowa, Iowa city, Iowa Johns Hopkins University, School of Public Health, Baltimore, Maryland, USA Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania Background: Orofacial clefts (OFC) are the most frequent congenital malformations of the head and neck, with birth prevalence approximately 1 in 700. They are commonly divided into cleft lip with or without cleft palate (CL(P)) and cleft palate (CP) groups based on anatomical, genetic, and embryological findings. Advances in the knowledge of OFC etiology have shown strong evidence of association with markers in candidate genes including Interferon regulatory factor six (IRF6), Forkehead boxE1 (FOXE1), and Muscle segment homeobox (MSX1). Recently, genome wide association studies (GWAS) of CL(P) have identified genetic associations for non-syndromic CL(P) on chromosome 8q24.21, and in or near the IRF6, ABCA4, and MAFB genes. Signals approaching GWAS significance were also observed in or near the PAX7, VAX1, and NTN1 genes. The present study investigated the presence of common and rare variants in PAX7 and VAX1 genes as a follow-up to the GWAS signals (Beaty et al., 2010). Methods: Direct sequencing was used to search for sequence variations in coding regions and conserved non-coding regions in and around the PAX7 and VAX1 genes in 360 individuals (90 Caucasian CL(P) cases and 90 controls, 90 Asian CL(P) cases and 90 controls). The observed variants were compared between cases and controls using the Fishers chi square test. Results: We found a total number of 16 new variants (three missense, two synonymous and eleven non-coding variants). Of those, two missense mutations in the PAX7 gene (G411R in Caucasians and G412S in Asians), both of them were observed in 1% the cases and none in the controls. G411R was predicted as possibly damaging of the protein structureby PolyPhen and G412S asprobably damaging. Also in the PAX7 gene, a missense mutation P397L predicted as benign by PolyPhen was observed only in 1% of Caucasian controls. Common variants in the PAX7 gene (rs4920523, P1⁄4 0.006 and rs1416464, P1⁄4 0.001 using the Fisher’s