title: The cell adhesion gene PVRL3 is associated with congenital ocular defects.
abstract: 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.
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Salil A
authors.initials: SA
authors.lastname: Lachke
authors.forename: Anne W
authors.initials: AW
authors.lastname: Higgins
authors.forename: Maiko
authors.initials: M
authors.lastname: Inagaki
authors.forename: Irfan
authors.initials: I
authors.lastname: Saadi
authors.forename: Qiongchao
authors.initials: Q
authors.lastname: Xi
authors.forename: Michelle
authors.initials: M
authors.lastname: Long
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Quade
authors.forename: Michael E
authors.initials: ME
authors.lastname: Talkowski
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Atsuko
authors.initials: A
authors.lastname: Fujimoto
authors.forename: Michael L
authors.initials: ML
authors.lastname: Robinson
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Quynh T
authors.initials: QT
authors.lastname: Duong
authors.forename: Irit
authors.initials: I
authors.lastname: Shapira
authors.forename: Benny
authors.initials: B
authors.lastname: Motro
authors.forename: Jun
authors.initials: J
authors.lastname: Miyoshi
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Morton
authors.forename: Richard L
authors.initials: RL
authors.lastname: Maas
mesh_terms: D000818:Animals; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D019457:Chromosome Breakage; D006801:Humans; D008214:Lymphocytes; D008297:Male; D051379:Mice; D009154:Mutation; D000072379:NIMA-Related Kinases; D000075983:Nectins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D015815:Cell Adhesion Molecules; C000619014:NECTIN3 protein, human; C000619017:Nectin3 protein, mouse; D000075983:Nectins; D000072379:NIMA-Related Kinases; C512686:Nek7 protein, mouse; D017346:Protein Serine-Threonine Kinases