Morgagnian cataract resulting from a naturally occurring nonsense mutation elucidates a role of CPAMD8 in mammalian lens development

by Anne K. Hollmann, Insa Dammann, Wiebke M. Wemheuer, Wilhelm E. Wemheuer, Almuth Chilla, Andrea Tipold, Walter J. Schulz-Schaeffer, Julia Beck, Ekkehard Sch ütz, Bertram Brenig To investigate the genetic basis of hereditary lens opacities we analyzed 31 cases of bilateral congenital cataract in Red Holstein Friesian cattle. A genome-wide association study revealed a significant association on bovine chromosome 7 at positions 6,166,179 and 12,429,691. Whole genome re-sequ encing of one case and four relatives showed a nonsense mutation (g.5995966C>T) in the PZP-like, alpha-2-macroglobulin domain containing 8 (CPAMD8) gene leading to a premature stop codon (CPAMD8 p.Gln74*) associated with cataract development in cattle. With immunohistochemistry we confirmed a physiological expression of CPAMD8 in the ciliary body epithelium of the eye in unaffected cattle, while the protein was not detectable in the ciliary body of cattle with cataracts. RNA expression ofCPAMD8 was detected in healthy adult, fetal and cataractous lenses.
Source: PLoS One - Category: Biomedical Science Authors: Source Type: research