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Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report

  • Authors:
    • Chengzi Huang
    • Xigui Long
    • Can Peng
    • Pengsiyuan Lin
    • Hu Tan
    • Weigang Lv
    • Lingqian Wu
  • View Affiliations / Copyright

    Affiliations: Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, P.R. China, Department of Medical Genetics, Hunan Jiahui Genetics Hospital, Changsha, Hunan 410078, P.R. China
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4711-4718
    |
    Published online on: April 11, 2019
       https://doi.org/10.3892/mmr.2019.10153
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Abstract

Autosomal recessive cornea plana is a very rare hereditary ocular disease, characterized by a flattened corneal curvature, marked hyperopia due to low refractive power and frequently consequent accommodative esotropia. Other features include various cornea anterior segment abnormalities, without systemic problems. The purpose of the present study was to investigate the clinical and molecular alterations in a Chinese family with cornea plana. Full ophthalmic examinations of the patients were performed, including slit‑lamp examination, fundus examination and ocular ultrasound. Whole‑exome sequencing data were screened for pathological variants in the proband, which were confirmed by Sanger sequencing. One novel missense mutation, c.242A>G (p.N81S) and another novel 7 base‑pair deletion mutation, c.772‑779del (p.G258Cfs*30), were detected in the keratocan (KERA) gene; two affected siblings inherited these variations in a compound heterozygous state, which were derived from the clinically unaffected heterozygous father (c.772_779del) and mother (c.242A>G), respectively. Neither mutation was observed in unrelated healthy controls (n=200). Multiple computer software predictions supported the pathogenicity of the two variants. Furthermore, protein modeling prediction was performed to better understand the molecular basis of cornea plana, particularly the importance of the leucine‑rich repeat domain. This study presents the 14th pathogenic KERA mutations identified worldwide and the first in East Asia so far, to the best of our knowledge. These findings guided prenatal diagnosis for the family in question and expand on the variant spectrum of KERA, therefore facilitating genetic counseling.
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1 

Pellegata NS, Dieguez-Lucena JL, Joensuu T, Lau S, Montgomery KT, Krahe R, Kivelä T, Kucherlapati R, Forsius H and de la Chapelle A: Mutations in KERA, encoding keratocan, cause cornea plana. Nat Genet. 25:91–95. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Khan AO, Aldahmesh M and Meyer B: Corneal ectasia and hydrops in a patient with autosomal recessive cornea plana. Ophthalmic Genet. 27:99–101. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Khan AO, Aldahmesh M and Meyer B: Recessive cornea plana in the Kingdom of Saudi Arabia. Ophthalmology. 113:1773–1778. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Khan AO, Aldahmesh MA, Al-Gehedan S, Meyer BF and Alkuraya FS: Corneal decompensation in recessive cornea plana. Ophthalmic Genet. 30:142–145. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Tahvanainen E, Forsius H, Kolehmainen J, Damsten M, Fellman J and de la Chapelle A: The genetics of cornea plana congenita. J Med Genet. 33:116–119. 1996. View Article : Google Scholar : PubMed/NCBI

6 

Lehmann OJ, El-ashry MF, Ebenezer ND, Ocaka L, Francis PJ, Wilkie SE, Patel RJ, Ficker L, Jordan T, Khaw PT and Bhattacharya SS: A novel keratocan mutation causing autosomal recessive cornea plana. Invest Ophthalmol Vis Sci. 42:3118–3122. 2001.PubMed/NCBI

7 

Khan AO, Al-Saif A and Kambouris M: A novel KERA mutation associated with autosomal recessive cornea plana. Ophthalmic Genet. 25:147–152. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Ebenezer ND, Patel CB, Hariprasad SM, Chen LL, Patel RJ, Hardcastle AJ and Allen RC: Clinical and molecular characterization of a family with autosomal recessive cornea plana. Arch Ophthalmol. 123:1248–1253. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Khan AO, Aldahmesh M, Al-Saif A and Meyer B: Pellucid marginal degeneration coexistent with cornea plana in one member of a family exhibiting a novel KERA mutation. Br J Ophthalmol. 89:1538–1540. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Liskova P, Hysi PG, Williams D, Ainsworth JR, Shah S, de la Chapelle A, Tuft SJ and Bhattacharya SS: Study of p.N247S KERA mutation in a British family with cornea plana. Mol Vis. 13:1339–1347. 2007.PubMed/NCBI

11 

AlBakri A and Khan AO: Regarding corneal decompensation in recessive cornea plana. Ophthalmic Genet. 37:350–351. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Tasheva ES, Funderburgh JL, Funderburgh ML, Corpuz LM and Conrad GW: Structure and sequence of the gene encoding human keratocan. DNA. 10:67–74. 1999.

13 

Kobe B and Deisenhofer J: The leucine-rich repeat: A versatile binding motif. Trends Biochem Sci. 19:415–421. 1994. View Article : Google Scholar : PubMed/NCBI

14 

Kobe B and Deisenhofer J: Proteins with leucine-rich repeats. Curr Opin Struct Biol. 5:409–416. 1995. View Article : Google Scholar : PubMed/NCBI

15 

Bella J, Hindle KL, McEwan PA and Lovell SC: The leucine-rich repeat structure. Cell Mol Life Sci. 65:2307–2333. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Kao WW and Liu CY: Roles of lumican and keratocan on corneal transparency. Glycoconj J. 19:275–285. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Liu CY, Shiraishi A, Kao CW, Converse RL, Funderburgh JL, Corpuz LM, Conrad GW and Kao WW: The cloning of mouse keratocan cDNA and genomic DNA and the characterization of its expression during eye development. J Biol Chem. 273:22584–22588. 1998. View Article : Google Scholar : PubMed/NCBI

18 

Liu CY, Birk DE, Hassell JR, Kane B and Kao WW: Keratocan-deficient mice display alterations in corneal structure. J Biol Chem. 278:21672–21677. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Forsius H, Damsten M, Eriksson AW, Fellman J, Lindh S and Tahvanainen E: Autosomal recessive cornea plana. A clinical and genetic study of 78 cases in Finland. Acta Ophthalmol Scand. 76:196–203. 1998. View Article : Google Scholar : PubMed/NCBI

20 

Dudakova L, Palos M, Hardcastle AJ and Liskova P: Corneal endothelial findings in a Czech patient with compound heterozygous mutations in KERA. Ophthalmic Genet. 35:252–254. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Roos L, Bertelsen B, Harris P, Bygum A, Jensen H, Grønskov K and Tümer Z: Case report: A novel KERA mutation associated with cornea plana and its predicted effect on protein function. BMC Med Genet. 16:402015. View Article : Google Scholar : PubMed/NCBI

22 

Kumari D, Tiwari A, Choudhury M, Kumar A, Rao A and Dixit M: A novel KERA mutation in a case of autosomal recessive cornea plana with primary angle-closure glaucoma. J Glaucoma. 25:e106–e109. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Dudakova L, Vercruyssen JHJ, Balikova I, Postolache L, Leroy BP, Skalicka P and Liskova P: Analysis of KERA in four families with cornea plana identifies two novel mutations. Acta Ophthalmol. 96:e87–e91. 2018. View Article : Google Scholar : PubMed/NCBI

24 

Khan AO: Corneal ectasia in a boy with homozygous KERA mutation. Ophthalmic Genet. 39:141–143. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Chen R, Im H and Snyder M: Whole-exome enrichment with the Roche nimbleGen SeqCap EZ exome library SR platform. Cold Spring Harb Protoc. 2015:634–641. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al: Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 17:405–424. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS and Sunyaev SR: A method and server for predicting damaging missense mutations. Nat Methods. 7:248–249. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Ng PC and Henikoff S: Predicting deleterious amino acid substitutions. Genome Res. 11:863–874. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Offord V, Coffey TJ and Werling D: LRRfinder: A web application for the identification of leucine-rich repeats and an integrative Toll-like receptor database. Dev Comp Immunol. 34:1035–1041. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Arnold K, Bordoli L, Kopp J and Schwede T: The SWISS-MODEL workspace: A web-based environment for protein structure homology modelling. Bioinformatics. 22:195–201. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Kobe B and Deisenhofer J: Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats. Nature. 366:751–756. 1993. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Huang C, Long X, Peng C, Lin P, Tan H, Lv W and Wu L: Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report. Mol Med Rep 19: 4711-4718, 2019.
APA
Huang, C., Long, X., Peng, C., Lin, P., Tan, H., Lv, W., & Wu, L. (2019). Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report. Molecular Medicine Reports, 19, 4711-4718. https://doi.org/10.3892/mmr.2019.10153
MLA
Huang, C., Long, X., Peng, C., Lin, P., Tan, H., Lv, W., Wu, L."Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report". Molecular Medicine Reports 19.6 (2019): 4711-4718.
Chicago
Huang, C., Long, X., Peng, C., Lin, P., Tan, H., Lv, W., Wu, L."Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report". Molecular Medicine Reports 19, no. 6 (2019): 4711-4718. https://doi.org/10.3892/mmr.2019.10153
Copy and paste a formatted citation
x
Spandidos Publications style
Huang C, Long X, Peng C, Lin P, Tan H, Lv W and Wu L: Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report. Mol Med Rep 19: 4711-4718, 2019.
APA
Huang, C., Long, X., Peng, C., Lin, P., Tan, H., Lv, W., & Wu, L. (2019). Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report. Molecular Medicine Reports, 19, 4711-4718. https://doi.org/10.3892/mmr.2019.10153
MLA
Huang, C., Long, X., Peng, C., Lin, P., Tan, H., Lv, W., Wu, L."Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report". Molecular Medicine Reports 19.6 (2019): 4711-4718.
Chicago
Huang, C., Long, X., Peng, C., Lin, P., Tan, H., Lv, W., Wu, L."Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report". Molecular Medicine Reports 19, no. 6 (2019): 4711-4718. https://doi.org/10.3892/mmr.2019.10153
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