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

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.

Progress toward discerning the genetics of cleft lip

“…PVRL2 is a transmembrane glycoprotein that belongs to the poliovirus receptor family. Mutations in a related protein, PVRL1, are known to cause the autosomal recessive Margarita Island clefting syndrome [44], and heterozygotes for the PVRL1 W185X mutation are thought to have increased risk for nonsyndromic CL/P [45]. TGFB1 mutations in humans have been found to cause the Camurati-Engelmann-syndrome [46], which is a progressive diaphyseal dysplasia that does not include an orofacial clefting phenotype, even though TGFB1 is expressed in the palate [47].…”

Nectines et nectines-like

“…Necl-5/PVR est le récep-teur du virus de la poliomyélite et nectine-1 le récepteur majeur des virus herpes simplex de types 1 et 2 [8,19]. Des mutations du gène nectine-1 sont responsables de malformations orofaciales accompagnées de retard mental [20]. Plus récemment, certains membres de cette famille ont été impliqués dans la physiopathologie des cancers.…”

Identification and characterization of two zebrafish nectin‐1 genes that are differentially expressed in the developing eye and brain

“…Mutations in the human nectin-1 gene are associated with the ZlotogoraOgü r syndrome and Margarita Island ectodermal dysplasia (Bustos et al, 1991;Suzuki et al, 2000;Sozen et al, 2001;Scapoli et al, 2006). These syndromes are characterized by sparse hair, scanty eyebrows, plantar hyperkeratosis, abnormal ears, dental anomalies, syndactyly, cleft lip with or without cleft palate, and occasionally mental retardation.…”