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Article Open Access

Mutation analysis of two families with inherited congenital cataracts

  • Authors:
    • Chang Liang
    • Han Liang
    • Yu Yang
    • Liu Ping
    • Qiao Jie
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, P.R. China, Department of Ophthalmology, Peking University Third Hospital, Beijing 100191, P.R. China
    Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 3469-3475
    |
    Published online on: May 22, 2015
       https://doi.org/10.3892/mmr.2015.3819
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Abstract

The present study aimed to identify the genetic mutations in two families affected with congenital cataracts. Detailed family histories and clinical data of the family members were recorded. The family members with affected phenotypes were recruited, and candidate gene sequencing was performed to determine the disease‑causing mutation. Bioinformatics analysis was performed to predict the function of the mutant gene. Green fluorescent protein‑tagged human wild‑type CRYAA and GJA8 were sub‑cloned, and the mutants were generated by site‑directed mutagenesis. A novel mutation, c.416T>C (p.L139P), in CRYAA and a known mutation, c.139G>A (p.D47N), in GJA8 were identified. These mutations co‑segregated with all affected individuals in each family and were not observed in the unaffected family members or in unrelated controls. The results of the bioinformatics analysis indicated that the amino acid at position 139 was highly conserved and that the p.L139P mutation was predicted to be damaging, as with p.D47N. Finally, overexpression of the two mutants revealed marked alterations, compared with the wild‑type proteins. These results extend the mutation spectrum of CRYAA and provides further evidence that the p.D47N mutation in GJA8 is a hot-spot mutation.
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1 

Bermejo E and Martínez-Frías ML: Congenital eye malformations: clinical-epidemiological analysis of 1,124,654 consecutive births in Spain. Am J Med Genet. 75:497–504. 1998. View Article : Google Scholar : PubMed/NCBI

2 

Haargaard B, Wohlfahrt J, Fledelius HC, Rosenberg T and Melbye M: A nationwide Danish study of 1027 cases of congenital/infantile cataracts: etiological and clinical classifications. Ophthalmology. 111:2292–2298. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Shiels A, Bennett TM and Hejtmancik JF: Cat-Map: putting cataract on the map. Mol Vis. 16:2007–2015. 2010.PubMed/NCBI

4 

Huang B and He W: Molecular characteristics of inherited congenital cataracts. Eur J Med Genet. 53:347–357. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Reddy MA, Francis PJ, Berry V, Bhattacharya SS and Moore AT: Molecular genetic basis of inherited cataract and associated phenotypes. Surv Ophthalmol. 49:300–315. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Hejtmancik JF: Congenital cataracts and their molecular genetics. Semin Cell Dev Biol. 19:134–149. 2008. View Article : Google Scholar :

7 

World Medical Association: World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA. 310:2191–2194. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Beyer EC, Ebihara L and Berthoud VM: Connexin mutants and cataracts. Front Pharmacol. 4:432013. View Article : Google Scholar : PubMed/NCBI

9 

Graw J: Genetics of crystallins: cataract and beyond. Exp Eye Res. 88:173–189. 2009. View Article : Google Scholar

10 

Hsu CD, Kymes S and Petrash JM: A transgenic mouse model for human autosomal dominant cataract. Invest Ophthalmol Vis Sci. 47:2036–2044. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Menko AS and Andley UP: αA-Crystallin associates with α6 integrin receptor complexes and regulates cellular signaling. Exp Eye Res. 91:640–651. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Sharma KK, Kumar RS, Kumar GS and Quinn PT: Synthesis and characterization of a peptide identified as a functional element in alphaA-crystallin. J Biol Chem. 275:3767–3771. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Devi RR, Yao W, Vijayalakshmi P, Sergeev YV, Sundaresan P and Hejtmancik JF: Crystallin gene mutations in Indian families with inherited pediatric cataract. Mol Vis. 14:1157–1170. 2008.PubMed/NCBI

14 

Gong B, Zhang LY, Pang CP, Lam DS and Yam GH: Trimethylamine N-oxide alleviates the severe aggregation and ER stress caused by G98R alphaA-crystallin. Mol Vis. 15:2829–2840. 2009.PubMed/NCBI

15 

Hansen L, Yao W, Eiberg H, et al: Genetic heterogeneity in microcornea-cataract: five novel mutations in CRYAA, CRYGD and GJA8. Invest Ophthalmol Vis Sci. 48:3937–3944. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Litt M, Kramer P, LaMorticella DM, Murphey W, Lovrien EW and Weleber RG: Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA. Hum Mol Genet. 7:471–474. 1998. View Article : Google Scholar : PubMed/NCBI

17 

Mackay DS, Andley UP and Shiels A: Cell death triggered by a novel mutation in the alphaA-crystallin gene underlies autosomal dominant cataract linked to chromosome 21q. Eur J Hum Genet. 11:784–793. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Raju I and Abraham EC: Congenital cataract causing mutants of alphaA-crystallin/sHSP form aggregates and aggresomes degraded through ubiquitin-proteasome pathway. PLoS One. 6:e280852011. View Article : Google Scholar

19 

Santhiya ST, Soker T, Klopp N, et al: Identification of a novel, putative cataract-causing allele in CRYAA (G98R) in an Indian family. Mol Vis. 12:768–773. 2006.PubMed/NCBI

20 

Zhang LY, Yam GH, Tam PO, et al: An alphaA-crystallin gene mutation, Arg12Cys, causing inherited cataract-microcornea exhibits an altered heat-shock response. Mol Vis. 15:1127–1138. 2009.PubMed/NCBI

21 

Goodenough DA: Lens gap junctions: a structural hypothesis for nonregulated low-resistance intercellular pathways. Invest Ophthalmol Vis Sci. 18:1104–1122. 1979.PubMed/NCBI

22 

Nielsen MS, Nygaard Axelsen L, Sorgen PL, Verma V, Delmar M and Holstein-Rathlou NH: Gap junctions. Compr Physiol. 2:1981–2035. 2012.

23 

Gong X, Li E, Klier G, Huang Q, Wu Y, Lei H, Kumar NM, Horwitz J and Gilula NB: Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice. Cell. 91:833–843. 1997. View Article : Google Scholar : PubMed/NCBI

24 

Rong P, Wang X, Niesman I, Wu Y, Benedetti LE, Dunia I, Levy E and Gong X: Disruption of Gja8 (alpha8 connexin) in mice leads to microphthalmia associated with retardation of lens growth and lens fiber maturation. Development. 129:167–174. 2002.PubMed/NCBI

25 

Li J, Wang Q, Fu Q, et al: A novel connexin 50 gene (gap junction protein, alpha 8) mutation associated with congenital nuclear and zonular pulverulent cataract. Mol Vis. 19:767–774. 2013.PubMed/NCBI

26 

Lin Y, Liu NN, Lei CT, et al: A novel GJA8 mutation in a Chinese family with autosomal dominant congenital cataract. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 25:59–62. 2008.PubMed/NCBI

27 

Wang L, Luo Y, Wen W, Zhang S and Lu Y: Another evidence for a D47N mutation in GJA8 associated with autosomal dominant congenital cataract. Mol Vis. 17:2380–2385. 2011.PubMed/NCBI

28 

Arora A, Minogue PJ, Liu X, et al: A novel connexin 50 mutation associated with congenital nuclear pulverulent cataracts. J Med Genet. 45:155–160. 2008. View Article : Google Scholar

29 

Minogue PJ, Tong JJ, Arora A, et al: A mutant connexin 50 with enhanced hemichannel function leads to cell death. Invest Ophthalmol Vis Sci. 50:5837–5845. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Sellitto C, Li L and White TW: Connexin 50 is essential for normal postnatal lens cell proliferation. Invest Ophthalmol Vis Sci. 45:3196–3202. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liang C, Liang H, Yang Y, Ping L and Jie Q: Mutation analysis of two families with inherited congenital cataracts. Mol Med Rep 12: 3469-3475, 2015.
APA
Liang, C., Liang, H., Yang, Y., Ping, L., & Jie, Q. (2015). Mutation analysis of two families with inherited congenital cataracts. Molecular Medicine Reports, 12, 3469-3475. https://doi.org/10.3892/mmr.2015.3819
MLA
Liang, C., Liang, H., Yang, Y., Ping, L., Jie, Q."Mutation analysis of two families with inherited congenital cataracts". Molecular Medicine Reports 12.3 (2015): 3469-3475.
Chicago
Liang, C., Liang, H., Yang, Y., Ping, L., Jie, Q."Mutation analysis of two families with inherited congenital cataracts". Molecular Medicine Reports 12, no. 3 (2015): 3469-3475. https://doi.org/10.3892/mmr.2015.3819
Copy and paste a formatted citation
x
Spandidos Publications style
Liang C, Liang H, Yang Y, Ping L and Jie Q: Mutation analysis of two families with inherited congenital cataracts. Mol Med Rep 12: 3469-3475, 2015.
APA
Liang, C., Liang, H., Yang, Y., Ping, L., & Jie, Q. (2015). Mutation analysis of two families with inherited congenital cataracts. Molecular Medicine Reports, 12, 3469-3475. https://doi.org/10.3892/mmr.2015.3819
MLA
Liang, C., Liang, H., Yang, Y., Ping, L., Jie, Q."Mutation analysis of two families with inherited congenital cataracts". Molecular Medicine Reports 12.3 (2015): 3469-3475.
Chicago
Liang, C., Liang, H., Yang, Y., Ping, L., Jie, Q."Mutation analysis of two families with inherited congenital cataracts". Molecular Medicine Reports 12, no. 3 (2015): 3469-3475. https://doi.org/10.3892/mmr.2015.3819
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