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

dc.creatorAvila, Joseph R.
dc.creatorJezewski, Peter A.
dc.creatorVieira, Alexandre R.
dc.creatorOrioli, Iêda M.
dc.creatorCastilla, Eduardo E.
dc.creatorChristensen, Kaare
dc.creatorDaack-Hirsch, Sandra
dc.creatorRomitti, Paul A.
dc.creatorMurray, Jeffrey C.
dc.date2019-12-26T12:14:34Z
dc.date2019-12-26T12:14:34Z
dc.date2006
dc.date.accessioned2023-09-26T23:48:08Z
dc.date.available2023-09-26T23:48:08Z
dc.identifierAVILA, Joseph R. et al. PVRL1 Variants Contribute to Non-Syndromic Cleft Lip and Palate in Multiple Populations. American Journal of Medical Genetics Part A, v. 140, n. 23, p. 2562-2570, Dec. 2006.
dc.identifier1552-4825
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/38821
dc.identifier10.1002/ajmg.a.31367
dc.identifier1552-4833
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8894367
dc.descriptionPoliovirus 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 G361V coding variant was significantly overtransmitted among all orofacial clefting phenotypes (P = 0.005). This represented G361V 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.
dc.description2022-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherWiley
dc.rightsrestricted access
dc.subjectLábio leporino não sindrômico
dc.subjectVariantes
dc.subjectFenda palatina
dc.subjectPoliovirus
dc.subjectPVRL1
dc.subjectVariants
dc.subjectNon-syndromic cleft lip
dc.subjectCleft palate
dc.titlePVRL1 variants contribute to non-syndromic cleft lip and palate in multiple populations
dc.typeArticle


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