Mutations of PVRL1, encoding a cell-cell adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal dysplasia


Cleft lip, with or without cleft palate (CL/P), is one of the most common birth defects, occurring in 0.4 to 2.0 per 1,000 infants born alive1. Approximately 70% of CL/P cases are non-syndromic (MIM 119530), but CL/P also occurs in many single-gene syndromes, each affecting a protein critical for orofacial development. Here we describe positional cloning of the gene responsible for an autosomal recessive CL/P-ectodermal dysplasia (ED) syndrome (CLPED1; previously ED4; ref. 2), which we identify as PVRL1, encoding nectin-1, an immunoglobulin (Ig)-related transmembrane cell-cell adhesion molecule that is part of the NAP cell adhesion system3,4,5,6. Nectin-1 is also the principal cell surface receptor for α-herpesviruses (HveC; ref. 7), and the high frequency of CLPED1 on Margarita Island in the Caribbean Sea might result from resistance of heterozygotes to infection by these viruses.

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Figure 1: Positional cloning of the CLPED1 locus.
Figure 2: PVRL1 mutations in CLPED1 patients.
Figure 3: Expression of Pvrl1 mRNA during mouse embryo development.

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We thank C. Jones for PAC p32o11; and D. Shukla and P.G. Spear for the unpublished mouse Pvrl1 cDNA sequence. This work was supported by grants from the March of Dimes Birth Defects Foundation (FY99-609) and the National Foundation for Ectodermal Dysplasia to R.A.S. and the National Institutes of Health (HD01079, DE12462) to J.A.H.

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Correspondence to Richard A. Spritz.

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Suzuki, K., Hu, D., Bustos, T. et al. Mutations of PVRL1, encoding a cell-cell adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal dysplasia. Nat Genet 25, 427–430 (2000).

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