title: Mutations in CTNNA1 cause butterfly-shaped pigment dystrophy and perturbed retinal pigment epithelium integrity.
abstract: Butterfly-shaped pigment dystrophy is an eye disease characterized by lesions in the macula that can resemble the wings of a butterfly. Here we report the identification of heterozygous missense mutations in the CTNNA1 gene (encoding α-catenin 1) in three families with butterfly-shaped pigment dystrophy. In addition, we identified a Ctnna1 missense mutation in a chemically induced mouse mutant, tvrm5. Parallel clinical phenotypes were observed in the retinal pigment epithelium (RPE) of individuals with butterfly-shaped pigment dystrophy and in tvrm5 mice, including pigmentary abnormalities, focal thickening and elevated lesions, and decreased light-activated responses. Morphological studies in tvrm5 mice demonstrated increased cell shedding and the presence of large multinucleated RPE cells, suggesting defects in intercellular adhesion and cytokinesis. This study identifies CTNNA1 gene variants as a cause of macular dystrophy, indicates that CTNNA1 is involved in maintaining RPE integrity and suggests that other components that participate in intercellular adhesion may be implicated in macular disease.
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Nicole T M
authors.initials: NT
authors.lastname: Saksens
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Krebs
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Frederieke E
authors.initials: FE
authors.lastname: Schoenmaker-Koller
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, USA.
authors.forename: Wanda
authors.initials: W
authors.lastname: Hicks
authors.affiliation: Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.|Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Minzhong
authors.initials: M
authors.lastname: Yu
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, USA.
authors.forename: Lanying
authors.initials: L
authors.lastname: Shi
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Rowe
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, USA.
authors.forename: Gayle B
authors.initials: GB
authors.lastname: Collin
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, USA.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Charette
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Stef J
authors.initials: SJ
authors.lastname: Letteboer
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Kornelia
authors.initials: K
authors.lastname: Neveling
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Tamara W
authors.initials: TW
authors.lastname: van Moorsel
authors.affiliation: Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Sleiman
authors.initials: S
authors.lastname: Abu-Ltaif
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Elfride
authors.initials: E
authors.lastname: De Baere
authors.affiliation: Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Walraedt
authors.affiliation: Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.|Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Banfi
authors.affiliation: Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, Second University of Naples, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonelli
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.|Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Camiel J F
authors.initials: CJ
authors.lastname: Boon
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Roepman
authors.affiliation: Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium.|Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.|Division of Ophthalmology, The Children's Hospital of Ophthalmology, Philadelphia, Pennsylvania, USA.|Center for Cellular and Molecular Therapeutics, The Children's Hospital of Ophthalmology, Philadelphia, Pennsylvania, USA.
authors.forename: Bart P
authors.initials: BP
authors.lastname: Leroy
authors.affiliation: Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.|Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.|Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors.forename: Neal S
authors.initials: NS
authors.lastname: Peachey
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, USA.
authors.forename: Patsy M
authors.initials: PM
authors.lastname: Nishina
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.|Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D008027:Light; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D020125:Mutation, Missense; D010375:Pedigree; D058499:Retinal Dystrophies / Q000235:genetics* / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D051178:alpha Catenin / Q000235:genetics*
chemical_list: C495273:CTNNA1 protein, human; D051178:alpha Catenin