Abstract
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 alive. 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 system. Nectin-1 is also the principal cell surface receptor for alpha-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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Cell Adhesion Molecules / genetics*
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Cleft Lip / genetics*
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Cleft Lip / pathology
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Cleft Palate / genetics*
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Cleft Palate / pathology
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DNA / chemistry
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DNA / genetics
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DNA Mutational Analysis
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Ectodermal Dysplasia / genetics*
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Ectodermal Dysplasia / pathology
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Embryo, Mammalian / metabolism
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Frameshift Mutation
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Gene Expression Regulation, Developmental
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Genes / genetics
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Homozygote
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Humans
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In Situ Hybridization
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Mice
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Mice, Inbred C3H
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Molecular Sequence Data
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Mutation
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Nectins
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
Substances
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Cell Adhesion Molecules
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NECTIN1 protein, human
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Nectin1 protein, mouse
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Nectins
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RNA, Messenger
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DNA
Associated data
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GENBANK/AF196761
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GENBANK/AF196762
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GENBANK/AF196763
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GENBANK/AF196764
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GENBANK/AF196765
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GENBANK/AF196766
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GENBANK/AF196767
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GENBANK/AF252867