Study of congenital Morgagnian cataracts in Holstein calves

Abstract

Cataracts are focal to diffuse opacities of the eye lens causing impaired vision or complete blindness. For bilateral congenital cataracts in Red Holsteins a perfectly cosegregating mutation within the CPAMD8 gene (CPAMD8:g.5995966C>T) has been reported. We genotyped the CPAMD8:g.5995966C>T variant in Holstein calves affected by congenital bilateral congenital cataracts, their unaffected relatives and randomly selected herd mates. Ophthalmological examinations were performed in all affected individuals to confirm a congenital cataract. Whole genome sequencing was employed to screen variants in candidate genes for the Morgagnian cataract phenotype. In the present study, 3/35 cases were confirmed as homozygous mutated and 6/14 obligate carriers. Further 7/46 unaffected animals related with these cases were heterozygous mutated for the CPAMD8:g.5995966C>T variant. However 32 cases with a congenital cataract showed the wild type for the CPAMD8 variant. We did not identify variants in the candidate genes CPAMD8 and NID1 or in their close neighborhood as strongly associated with the congenital cataract phenotype in Holstein calves with the CPAMD8 wild type. In conclusion, the CPAMD8:g.5995966C>T variant is insufficient to explain the majority of Morgagnian congenital cataract phenotypes in Holsteins. It is very likely that congenital bilateral cataracts may be genetically heterogeneous and not yet known variants in genes other than CPAMD8 and NID1 are involved.

Fig 1. Bovine congenital bilateral cataract in Holstein calves.

(A) The right and (B) the left eye of a Red Holstein calf from farm A with congenital opacities of the lens. The right (C) and the left eye (D) with opaque lenses of a polled Holstein calf from farm C are displayed.

Fig 2. Gross findings in calves with congenital cataracts.

(A) Cross section through the globe of case no. 5. (B) Anterior view of the isolated lens of case no. 6. Lenses show areas of turbidity in nuclear and cortical areas (asterisks). In addition, both lenses show a rupture of the anterior capsule with protrusion of lens material (areas delineated by arrows).

Fig 3. Histologic lesions in lenses from calves with congenital cataracts.

Hematoxylin-eosin stain. Scale bars: A-C: 50 μm, D-F: 25 μm. (A) Intact anterior pole in a less affected calf (1) regular lens capsule (2) lens epithelium and (3) parallel lens fibers (case 4). (B) Posterior lens pole shows wrinkling of the capsule (arrow) and prominent subcapsular fibrosis (asterisk, case 5). (C) Gradual degeneration of lens fibers in the nucleus: (1) preserved fibers (2) fiber denaturation with formation of Morgagnian globules, (3) complete liquefaction of fibers into amorphous eosinophilic fluid (case 4). (D) Higher magnification of Morgagnian globules in the lens of (case 5). (E) Lenticular degeneration is accompanied by accumulation of bladder cells (case 6). (F) Dystrophic mineralization occurring in cataractous lesions (basophilic, granular material marked by arrows in case 6).

Fig 4

Pedigree analysis of animals from farm A, B and C. The affected calves showed congenital bilateral cataract. In farm C, all sires of affected calves were genetically polled insemination bulls. These sires could be traced back to a common ancestor, a heterozygous polled Red Holstein bull. Cases 1–6 were ophthalmologically and pathologically examined. Other cases underwent an ophthalmological examination. Asterisks mark animals used for whole genome sequencing.