molecule/herpesv irus 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 syn- dromes, each affecting a protein critical for orofacial develop- ment. Here we describe positional cloning of the gene responsible for an autosomal recessive CL/P-ectodermal dysplasia (ED) syn- drome (CLPED1; previously ED4; ref. 2), which we identify as PVRL1, encoding nectin-1, an immunoglobulin (Ig)-related trans- membrane cell-cell adhesion molecule that is part of the NAP cell adhesion system3-6. 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. CLPED1, which includes Zlotogora-Ogur syndrome 8-12 (MIM 225000) and Margarita Island ED (MIM 225060; ref. 13), is char- acterized clinically by CL/P, hidrotic ED, developmental defects of the hands and, in some cases, mental retardation. Although generally rare, CLPED1 occurs with a frequency of approxi- mately 1 per 2,000 among the indigenous population of Mar- garita Island 2,13 , in whom we previously assigned the CLPED1 locus to an approximately 1-2-Mb interval in 11q23 (ref. 2). To