Mutations in CTNNA1 cause butterfly-shaped pigment dystrophy and perturbed retinal pigment epithelium integrity.
Document Type
Article
Publication Date
2-2016
JAX Source
Nat Genet 2016 Feb; 48(2):144-51.
Volume
48
Issue
2
First Page
144
Last Page
151
ISSN
1546-1718
PMID
26691986
Grant
EY016501, CA34196
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. Nat Genet 2016 Feb; 48(2):144-51.
Recommended Citation
Saksens N,
Krebs MP,
Schoenmaker-Koller F,
Hicks WL,
Yu M,
Shi L,
Rowe LB,
Collin GB,
Charette JR,
Letteboer S,
Neveling K,
van Moorsel T,
Abu-Ltaif S,
De Baere E,
Walraedt S,
Banfi S,
Simonelli F,
Cremers F,
Boon C,
Roepman R,
Leroy B,
Peachey N,
Hoyng C,
Nishina PM,
den Hollander A.
Mutations in CTNNA1 cause butterfly-shaped pigment dystrophy and perturbed retinal pigment epithelium integrity. Nat Genet 2016 Feb; 48(2):144-51.