The cell adhesion gene PVRL3 is associated with congenital ocular defects

Salil A. Lachke, Anne W. Higgins, Maiko Inagaki, Irfan Saadi, Qiongchao Xi, Michelle Long, Bradley J. Quade, Michael E. Talkowski, James F. Gusella, Atsuko Fujimoto, Michael L. Robinson, Ying Yang, Quynh T. Duong, Irit Shapira, Benny Motro, Jun Miyoshi, Yoshimi Takai, Cynthia C. Morton, Richard L. Maas

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish
Pages (from-to)235-250
Number of pages16
JournalHuman Genetics
Issue number2
StatePublished - Feb 2012

Bibliographical note

Funding Information:
Acknowledgments We thank the subject and his relatives for participating in the Developmental Genome Anatomy Project and Heather Ferguson, Chantal Kelly and Shahrin Ahsan for assistance as study coordinators. This work was supported by NIH grants 5R01EY10123-15 (RLM), 5R01HD060050-02 (RLM), 5P01GM061354-07 (CCM, RLM, JFG, BJQ), R01EY021505 (SAL), R01EY12995 (MLR), and T35-EY07151 (QTD). All experiments comply with the current laws of the countries (US, Israel and Japan) in which they were performed.


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