Mutations in crystallin genes result in congenital cataract associated with other ocular abnormalities

Abstract

Purpose: This study aims to describe the phenotypes and identify pathogenic mutations in Chinese patients who have congenital cataracts associated with other ocular abnormalities.

Methods: Eleven patients from four unrelated Chinese families plus two simplex cases were enrolled in this study. Detailed ophthalmic examinations were performed. DNA samples were isolated from peripheral blood collected from the patients. Next-generation sequencing of known ocular genes was applied to the proband of each family and two simplex cases to find pathogenic variances. PCR and Sanger sequencing were conducted for validation and segregation tests.

Results: All 13 patients had congenital cataracts, and other ocular abnormalities were found in some cases. Microcornea was found in 12 subjects, and ocular coloboma was observed in five. Various types of coloboma, including iris, choroid, macular, and optic disc, were described. Five mutations in crystallin genes were identified. Four of the mutations are novel: CRYBB1: p.(Arg230Cys), CRYBB2: p.(Gly149Val), CRYGC: p.(Met44CysfsTer59), and CRYGC: p.(Tyr144Ter). One mutation was reported previously: CRYAA: p.(Arg21Trp).

Conclusions: We examined a cohort of Chinese patients with congenital cataracts and studied the phenotypes and genotypes. Extralenticular abnormalities, such as microcornea and ocular coloboma, can also be found in patients with congenital cataracts. The phenotype of congenital cataracts associated with macular and optic disc coloboma was reported for the first time in this study. Four novel mutations and one previously reported mutation were identified. These data expand the mutation spectrum in crystallin genes and enhance our understanding of the phenotypes of congenital cataracts.

Figure 2

Ocular photographs of patient II:1 from family A. A and B: Photographs of the anterior segment of the left eye, showing a congenital nuclear cataract. C and D: Fundus photographs of the right and left eyes, respectively, showing optic disc coloboma for both eyes and macular coloboma for the right eye.

Figure 3

B-ultrasonography images of patients from family B. A and B: Images of the right and left eyes, respectively of patient II:2. C and D: Images of the right and left eyes, respectively, of patient III:1. The B-ultrasonography images show posterior segment coloboma for both eyes of patient II:2 and the right eye of patient III:1. Focal and irregular introcessions in the eyeball wall are marked with red arrows.

Figure 4

Fundus photographs of simplex case 2. A: Right eye. B: Left eye. The fundus photographs of simplex case 2 show optic disc coloboma for the right eye and a relatively normal phenotype for the left eye.

Figure 1

Pedigrees of four Chinese families. A–D: Pedigrees of family A through family D, respectively. Squares and circles indicate men and women, respectively. Filled and empty symbols indicate affected and unaffected members, respectively. Deceased individuals are indicated with slashes. Probands are indicated with arrows.

Figure 5

Chromatograms of all detected mutations. A: Sequence for patient III:2 from family A. B: Sequence for patient III:1 from family B. C: Sequence for patient II:1 from family C. D: Sequence for patient II:1 from family D. E: Sequence for simplex case 1. F: Sequence for simplex case 2. The arrow indicates the mutation.