Biomaterial Database

The cell adhesion gene PVRL3 is associated with congenital ocular defects. 2012

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

Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

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.

UI	MeSH Term	Description	Entries
D008214	Lymphocytes	White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.	Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008297	Male		Males
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D002386	Cataract	Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed)	Cataract, Membranous,Lens Opacities,Pseudoaphakia,Cataracts,Cataracts, Membranous,Lens Opacity,Membranous Cataract,Membranous Cataracts,Opacities, Lens,Opacity, Lens,Pseudoaphakias
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072379	NIMA-Related Kinases	A highly conserved family of protein serine-threonine kinases that regulate the CELL CYCLE; MITOSIS; and the response to DNA DAMAGE. They are also involved in the assembly and function of microtubule-based structures such as CILIA and CENTRIOLES.	NEK Family Kinase,NEK Kinase,NIMA Family Kinase,NIMA-Related Kinase,Never-in-Mitosis A Kinase,NEK Family Kinases,NEK Kinases,NIMA Family Kinases,NIMA Protein Kinase,NIMA-Related Protein Kinase,Never-in-Mitosis A Kinases,A Kinase, Never-in-Mitosis,Family Kinase, NEK,Family Kinase, NIMA,Kinase, NEK,Kinase, NEK Family,Kinase, NIMA Family,Kinase, NIMA-Related,Kinase, Never-in-Mitosis A,Kinases, NEK,Kinases, NEK Family,Kinases, NIMA Family,Kinases, NIMA-Related,Kinases, Never-in-Mitosis A,NIMA Related Kinase,NIMA Related Kinases,NIMA Related Protein Kinase,Never in Mitosis A Kinase,Never in Mitosis A Kinases
D000075983	Nectins	A family of calcium-independent cell adhesion molecules of the immunoglobulin superfamily. They are expressed by most cell types and mediate both homotypic and heterotypic cell-cell adhesion. Nectins function in a variety of morphogenetic and developmental processes that include organogenesis of the eye, ear, tooth, and cerebral cortex; they also play roles in viral infection and cell proliferation.	CD111 Antigen,CD112 Antigen,CD113 Antigen,Herpesvirus Entry Mediator C,HevC Protein,Human Poliovirus Receptor Related 1,Nectin,Nectin-1,Nectin-1delta,Nectin-2,Nectin-2alpha,Nectin-2delta,Nectin-2gamma,Nectin-3,Nectin1delta,PVRL1,Poliovirus Receptor-Related Protein 1,Prr1 Protein,Antigen, CD111,Antigen, CD112,Antigen, CD113,Nectin 1,Nectin 1delta,Nectin 2,Nectin 2alpha,Nectin 2delta,Nectin 2gamma,Nectin 3,Poliovirus Receptor Related Protein 1
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014178	Translocation, Genetic	A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.	Chromosomal Translocation,Translocation, Chromosomal,Chromosomal Translocations,Genetic Translocation,Genetic Translocations,Translocations, Chromosomal,Translocations, Genetic