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

Anne K Hollmann; Insa Dammann; Wiebke M Wemheuer; Wilhelm E Wemheuer; Almuth Chilla; Andrea Tipold; Walter J Schulz-Schaeffer; Julia Beck; Ekkehard Schütz; Bertram Brenig

doi:10.1371/journal.pone.0180665

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

PLoS One. 2017 Jul 6;12(7):e0180665. doi: 10.1371/journal.pone.0180665. eCollection 2017.

Affiliations

¹ University of Goettingen, Institute of Veterinary Medicine, Goettingen, Germany.
² University Medical Center Goettingen, Department of Neuropathology, Prion and Dementia Research Unit, Goettingen, Germany.
³ University of the Saarland, Institute of Neuropathology, Homburg, Germany.
⁴ University of Veterinary Medicine Hannover, Foundation, Department of Small Animal Medicine and Surgery, Hannover, Germany.
⁵ Chronix Biomedical, Goettingen, Germany.

Abstract

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-sequencing 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 of CPAMD8 was detected in healthy adult, fetal and cataractous lenses.

MeSH terms

Animals
Cataract / genetics
Cataract / veterinary*
Cattle
Chromosome Mapping
Codon, Nonsense*
Female
Immunohistochemistry
Lens, Crystalline / growth & development*
alpha-Macroglobulins / physiology*

Substances

Codon, Nonsense
alpha-Macroglobulins

Grants and funding

We acknowledge support by the German Research Foundation and the Open Access Publication Funds of the University of Goettingen. The German Research Foundation and the Open Access Publication Funds of the University of Goettingen only cover the publication costs and did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.