PVRL1 variants contribute to non-syndromic cleft lip and palate in multiple populations

Avila, JR and Jezewski, PA and Vieira, AR and Orioli, IM and Castilla, EE and Christensen, K and Daack-Hirsch, S and Romitti, PA and Murray, JC (2006) PVRL1 variants contribute to non-syndromic cleft lip and palate in multiple populations. American Journal of Medical Genetics, Part A, 140 (23). 2562 - 2570. ISSN 1552-4825

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Abstract

Poliovirus Receptor Like-1 (PVRL1) is a member of the immunoglobulin super family that acts in the initiation and maintenance of epithelial adherens junctions and is mutated in the cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1, OMIM #225000). In addition, a common non-sense mutation in PVRL1 was discovered more often among non-syndromic sporadic clefting cases in Northern Venezuela in a previous case-control study. The present work sought to ascertain the role of PVRL1 in the sporadic forms of orofacial clefting in multiple populations. Multiple rare and common variants from all three splice isoforms were initially ascertained by sequencing 92 Iowan and 86 Filipino cases and CEPH controls. Using a family-based analysis to examine these variants, the common glycine allele of the G301V coding variant was significantly overtransmitted among all orofacial clefting phenotypes (P = 0.005). This represented G301V genotyping from over 800 Iowan, Danish, and Filipino families. Among four rare amino acid changes found within the V1 and C1 domains, S112T and T131A were found adjacent to critical amino acid positions within the V1 variable domain, regions previously shown to mediate cell-to-cell and cell-to-virus adhesion. The T131A variant was not found in over 1,300 non-affected control samples although the alanine is found in other species. The serine of the S112T variant position is conserved across all known PVRL1 sequences. Together these data suggest that both rare and common mutations within PVRL1 make a minor contribution to disrupting the initiation and regulation of cell-to-cell adhesion and downstream morphogenesis of the embryonic face. © 2006 Wiley-Liss, Inc.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Avila, JR Jezewski, PA Vieira, AR arv11@pitt.edu ARV11 Orioli, IM Castilla, EE Christensen, K Daack-Hirsch, S Romitti, PA Murray, JC
Date:	1 December 2006
Date Type:	Publication
Journal or Publication Title:	American Journal of Medical Genetics, Part A
Volume:	140
Number:	23
Page Range:	2562 - 2570
DOI or Unique Handle:	10.1002/ajmg.a.31367
Schools and Programs:	School of Dental Medicine > Dental Science
Refereed:	Yes
ISSN:	1552-4825
MeSH Headings:	Alleles; Amino Acid Sequence; Cell Adhesion Molecules--genetics; Cell Adhesion Molecules--metabolism; Cleft Lip--ethnology; Cleft Lip--genetics; Cleft Palate--ethnology; Cleft Palate--genetics; DNA Mutational Analysis; Genetic Variation; Humans; Linkage Disequilibrium; Molecular Sequence Data; Mutation; Population--genetics
Other ID:	NLM NIHMS15305, NLM PMC1885468
PubMed Central ID:	PMC1885468
PubMed ID:	17089422
Date Deposited:	20 Sep 2012 20:35
Last Modified:	20 Feb 2020 13:55
URI:	http://d-scholarship.pitt.edu/id/eprint/14228

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