Related Experiment Videos
Mutations of PVRL1, encoding a cell-cell adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal
1Human Medical Genetics Program, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Insights
Cleft lip and palate (CL/P) is a common birth defect. Researchers identified PVRL1, encoding nectin-1, as the gene responsible for a CL/P and ectodermal dysplasia syndrome, potentially offering viral resistance.
Area of Science:
- Genetics
- Developmental Biology
- Cell Biology
Background:
- Cleft lip, with or without cleft palate (CL/P), is a frequent congenital birth defect affecting 0.4–2.0 per 1,000 live births.
- While most CL/P cases are non-syndromic, some are linked to single-gene mutations impacting orofacial development.
- CL/P is also associated with ectodermal dysplasia (ED) syndromes, highlighting genetic factors in craniofacial development.
Purpose of the Study:
- To identify the genetic cause of an autosomal recessive cleft lip/palate-ectodermal dysplasia syndrome (CLPED1).
- To elucidate the role of the identified gene in orofacial development and its potential link to viral interactions.
Main Methods:
- Positional cloning was employed to identify the causative gene for CLPED1.
- The study involved genetic analysis and characterization of the identified gene and its protein product.
Main Results:
- The gene responsible for CLPED1 was identified as PVRL1, which encodes nectin-1.
- Nectin-1 is an immunoglobulin (Ig)-related transmembrane cell-cell adhesion molecule and a key component of the NAP cell adhesion system.
- Nectin-1 also functions as the primary cell surface receptor for alpha-herpesviruses (HveC).
Conclusions:
- The identification of PVRL1 as the gene for CLPED1 provides critical insight into the genetic basis of syndromic CL/P.
- Nectin-1's dual role in cell adhesion and viral receptor function suggests a potential evolutionary advantage for heterozygotes, possibly conferring resistance to alpha-herpesvirus infections.
- The high prevalence of CLPED1 on Margarita Island may be attributed to this heterozygote advantage against viral pathogens.
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.