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 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.
Human Medical Genetics Program, University of Colorado Health Sciences Center, Denver, Colorado, USA.
K
K
Suzuki
D
D
Hu
T
T
Bustos
J
J
Zlotogora
A
A
Richieri-Costa
J A
JA
Helms
R A
RA
Spritz
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics* / Q000473:pathology; D002972:Cleft Palate / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000473:pathology; D004622:Embryo, Mammalian / Q000378:metabolism; D016368:Frameshift Mutation; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009154:Mutation; D000075983:Nectins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D012333:RNA, Messenger; D004247:DNA