Mutations in CTNNA1 cause butterfly-shaped pigment dystrophy and perturbed retinal pigment epithelium integrity.

Nicole T M Saksens
Mark P. Krebs, The Jackson Laboratory
Frederieke E Schoenmaker-Koller
Wanda L. Hicks, The Jackson Laboratory
Minzhong Yu
Lanying Shi
Lucy B. Rowe, The Jackson Laboratory
Gayle B. Collin, The Jackson Laboratory
Jeremy R. Charette, The Jackson Laboratory
Stef J Letteboer
Kornelia Neveling
Tamara W van Moorsel
Sleiman Abu-Ltaif
Elfride De Baere
Sophie Walraedt
Sandro Banfi
Francesca Simonelli
Frans P M Cremers
Camiel J F Boon
Ronald Roepman
Bart P Leroy
Neal S Peachey
Carel B Hoyng
Patsy M. Nishina, The Jackson Laboratory
Anneke I den Hollander


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 2015 Dec 21 [Epub ahead of print]