The cell adhesion gene PVRL3 is associated with congenital ocular defects

• Published in: Human genetics Vol. 131; no. 2; pp. 235 - 250
• Main Authors: Lachke, Salil A., Higgins, Anne W., Inagaki, Maiko, Saadi, Irfan, Xi, Qiongchao, Long, Michelle, Quade, Bradley J., Talkowski, Michael E., Gusella, James F., Fujimoto, Atsuko, Robinson, Michael L., Yang, Ying, Duong, Quynh T., Shapira, Irit, Motro, Benny, Miyoshi, Jun, Takai, Yoshimi, Morton, Cynthia C., Maas, Richard L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.02.2012; Springer; Springer Nature B.V
• Subjects: Animals; Biology; Biomedical and Life Sciences; Biomedicine; Breakpoints; Cataract - congenital; Cataract - genetics; Cataracts; Cell adhesion; Cell adhesion & migration; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Line; Central nervous system; Child development; Chromosome 1; chromosome 3; Chromosome Breakage; Chromosome translocations; Data processing; Development; Embryos; Fluorescence in situ hybridization; Gene Function; Gene mapping; Genes; Genetic aspects; Genetic disorders; Genetic research; Genomics; Genotype & phenotype; Hospitals; Human Genetics; Humans; Inversion; Kinases; Lymphocytes; Male; Medical schools; Metabolic Diseases; Mice; Molecular Medicine; Mutation; nectin; Nectins; NIMA-Related Kinases; Original Investigation; Pathology; Polymerase chain reaction; Position effects; Protein Serine-Threonine Kinases - metabolism; Proteins; Retina; Transcription; Translocation, Genetic; United States > US; Massachusetts; Ocular Defect; Ciliary Body; Fiber Cell; Ciliary Epithelium; Lens Development
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-011-1064-z

We describe a male patient (patient DGAP113) with a balanced translocation, 46,XY,t(1;3)(q31.3;q13.13), severe bilateral congenital cataracts, CNS abnormalities and mild developmental delay. Fluorescence in situ hybridization (FISH) and suppression PCR demonstrated that the chromosome 3 breakpoint lies ~515 kb upstream of the PVRL3 gene, while the chromosome 1 breakpoint lies ~50 kb upstream of the NEK7 gene. Despite the fact that NEK7 is closer to a translocation breakpoint than PVRL3 , NEK7 transcript levels are unaltered in patient DGAP113 lymphoblastoid cells and Nek7 -deficient mice exhibit no detectable ocular phenotype. In contrast, the expression of PVRL3 , which encodes the cell adhesion protein Nectin 3, is significantly reduced in patient DGAP113 lymphoblastoid cells, likely due to a position effect caused by the chromosomal translocation. Nectin 3 is expressed in the mouse embryonic ciliary body and lens. Moreover, Pvrl3 knockout mice as well as a spontaneous mouse mutant ari (anterior retinal inversion), that maps to the Pvrl3 locus, exhibit lens and other ocular defects involving the ciliary body. Collectively, these data identify PVRL3 as a critical gene involved in a Nectin-mediated cell–cell adhesion mechanism in human ocular development.