Novel mutations associated with autosomal‑dominant congenital cataract identified in Chinese families

  • Authors:
    • Zhenyu Wang
    • Chen Huang
    • Yanxiu Sun
    • Huibin Lv
    • Mingzhou Zhang
    • Xuemin Li
  • View Affiliations

  • Published online on: August 8, 2019     https://doi.org/10.3892/etm.2019.7865
  • Pages: 2701-2710
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Abstract

As the leading cause of impaired vision, congenital cataracts, particularly autosomal dominant congenital cataract (ADCC), have been considered as a hereditary disease. The present study aimed to identify genetic defects in Chinese pedigrees with ADCC. A total of 6 Chinese families with ADCC were included, comprising 103 members and 27 patients assessed in total. Genomic DNA samples were extracted from the peripheral blood of probands; mutations were determined using a specific eye disease enrichment panel with next‑generation sequencing. Following pathogenicity prediction, sites with notable pathogenicity were screened for further validation. Sanger sequencing was performed in the remaining individuals of the families and 100 normal controls. The pathogenic effects of the mutations, including amino acid substitutions, as well as structural and functional alterations of proteins linked to ADCC, were investigated via bioinformatics analysis. A total of seven mutations in six candidate genes associated with ADCC were identified in the 6 families: Myosin heavy chain 9 (MYH9) c.4150G>C, β‑crystallin A4 (CRYBA4) c.169T>C, RPGR‑interacting protein 1 (RPGRRIP1) c.2669G>A, wolframin (WFS1) c.1235T>C, CRYBA4 c.26C>T, Ephrin receptor subfamily 2 (EPHA2) c.2663+1G>A and paired box 6 (PAX6) c.11‑2A>G. The seven mutations were only detected in affected individuals. Among them, there were three novel mutations (MYH9: c.4150G>C; CRYBA4: c.169T>C; RPGRRIP1: c.2669G>A) and four previously reported ones. Mutations in RPGRIP1 (c.2669G>A) and CRYBA4 (c.26C>T) were predicted to be benign according to bioinformatics analysis. Conversely, other mutations in EPHA2, PAX6, MYH9, CRYBA4 (c.169T>C) and WFS1 were determined to be pathogenic. The present study reported two novel heterozygous mutations (MYH9 c.4150G>C and CRYBA4 c.169T>C) identified by analyzing 6 Chinese families with ADCC, supporting their important roles in the development of the disease.

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October 2019
Volume 18 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
APA
Wang, Z., Huang, C., Sun, Y., Lv, H., Zhang, M., & Li, X. (2019). Novel mutations associated with autosomal‑dominant congenital cataract identified in Chinese families. Experimental and Therapeutic Medicine, 18, 2701-2710. https://doi.org/10.3892/etm.2019.7865
MLA
Wang, Z., Huang, C., Sun, Y., Lv, H., Zhang, M., Li, X."Novel mutations associated with autosomal‑dominant congenital cataract identified in Chinese families". Experimental and Therapeutic Medicine 18.4 (2019): 2701-2710.
Chicago
Wang, Z., Huang, C., Sun, Y., Lv, H., Zhang, M., Li, X."Novel mutations associated with autosomal‑dominant congenital cataract identified in Chinese families". Experimental and Therapeutic Medicine 18, no. 4 (2019): 2701-2710. https://doi.org/10.3892/etm.2019.7865