A novel mutation of FOXC1 in a Chinese family with Axenfeld‑Rieger syndrome

  • Authors:
    • Xing Wu
    • Hai‑Nan Xie
    • Tong Wu
    • Wei Liu
    • Lan‑Lam Chen
    • Zhao‑Hui Li
    • Da‑Jiang Wang
    • Yi Wang
    • Hou‑Bin Huang
  • View Affiliations

  • Published online on: July 18, 2019     https://doi.org/10.3892/etm.2019.7789
  • Pages: 2255-2261
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Axenfeld‑Rieger syndrome (ARS) is a disorder affecting the anterior segment of the eye and causing systemic malformations, and follows an autosomal‑dominant inheritance pattern. The aim of the present study was to identify the underlying cause of ARS in a Chinese family. Genomic DNA was extracted from the peripheral blood of the subjects from a family with ARS. The pathogenic variant was identified by targeted next‑generation sequencing and confirmed by Sanger sequencing. A novel heterozygous mutation of the forkhead box (FOX)C1 gene (c.1494delG, p.G499Afs*20) was detected in all affected members of the family, while no mutation was identified in the unaffected members or in the 150 normal controls. The affected members exhibited typical ocular and craniofacial anomalies. The results of the present study demonstrated that a novel deletion in exon 1 of the FOXC1 gene caused ARS in this Chinese family.

References

1 

Hjalt TA and Semina EV: Current molecular understanding of Axenfeld-Rieger syndrome. Expert Rev Mol Med. 7:1–17. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Millá E, Mañé B, Duch S, Hernan I, Borràs E, Planas E, Dias Mde S, Carballo M and Gamundi MJ; Spanish Multicenter Glaucoma Group-Estudio Multicéntrico Español de Investigación Genética del Glaucoma, EMEIGG, : Survey of familial glaucoma shows a high incidence of cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in non-consanguineous congenital forms in a Spanish population. Mol Vis. 19:1707–1722. 2013.PubMed/NCBI

3 

Espinoza HM, Cox CJ, Semina EV and Amendt BA: Amolecular basis for differential developmental anomalies in Axenfeld-Rieger syndrome. Hum Mol Genet. 11:743–753. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Reis LM, Tyler RC, Volkmann Kloss BA, Schilter KF, Levin AV, Lowry RB, Zwijnenburg PJ, Stroh E, Broeckel U, Murray JC and Semina EV: PITX2 and FOXC1 spectrum of mutations in ocular syndromes. Eur J Hum Genet. 20:1224–1233. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Challa P: Glaucoma genetics. Int Ophthalmol Clin. 48:73–94. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Gage PJ and Camper SA: Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation. Hum Mol Genet. 6:457–464. 1997. View Article : Google Scholar : PubMed/NCBI

7 

Tümer Z and Bach-Holm D: Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. Eur J Hum Genet. 17:1527–1539. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Cox MP, Peterson DA and Biggs PJ: SolexaQA: At-a-glance quality assessment of Illumina second-generation sequencing date. BMC Bioinformatics. 11:4852010. View Article : Google Scholar : PubMed/NCBI

9 

Li H and Durbin R: Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 25:1754–1760. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Wang K, Li M and Hakonarson H: ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38:e1642010. View Article : Google Scholar : PubMed/NCBI

11 

Seifi M and Walter MA: Axenfeld-Rieger syndrome. Clin Genet. 93:1123–1130. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Micheal S, Siddiqui SN, Zafar SN, Venselaar H, Qamar R, Khan MI and den Hollander AI: Whole exome sequencing identifies a heterozygous missense variant in the PRDM5 gene in a family with Axenfeld-Rieger syndrome. Neurogenetics. 17:17–23. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Riise R, D'haene B, De Baere E, Grønskov K and Brøndum-Nielsen K: Rieger syndrome is not associated with PAX6 deletion: A correction to Acta. Ophthalmol Scand 2001:79: 201–203. Acta Ophthalmol. 87:9232009. View Article : Google Scholar : PubMed/NCBI

14 

Kim GN, Ki CS, Seo SW, Yoo JM, Han YS, Chung IY, Park JM and Kim SJ: A novel forkhead box C1 gene mutation in a Korean family with Axenfeld-Rieger syndrome. Mol Vis. 19:935–943. 2013.PubMed/NCBI

15 

Kawase C, Kawase K, Taniguchi T, Sugiyama K, Yamamoto T, Kitazawa Y, Alward KL, Stone EM, Nishimura DY and Sheffield VC: Screening for mutations of Axenfeld-Rieger syndrome caused by FOXC1 gene in Japanese patients. J Glaucoma. 10:477–482. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Saleem RA, Banerjee-Basu S, Berry FB, Baxevanis AD and Walter MA: Structural and functional analyses of disease-causing missense mutations in the forkhead domain of FOXC1. Hum Mol Genet. 12:2993–3005. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Suzuki T, Takahashi K, Kuwahara S, Wada Y, Abe T and Tamai M: A novel (Pro79Thr) mutation in the FKHL7 gene in a Japanese family with Axenfeld-Rieger syndrome. Am J Ophthalmol. 132:572–575. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Strungaru MH, Dinu I and Walter MA: Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations. Invest Ophthalmol Vis Sci. 48:228–237. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Seifi M, Footz T, Taylor SA and Walter MA: Comparison of bioinformatics prediction, molecular modeling, and functional analyses of FOXC1 mutations in patients with Axenfeld-Rieger syndrome. Hum Mutat. 38:169–179. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Honkanen RA, Nishimura DY, Swiderski RE, Bennett SR, Hong S, Kwon YH, Stone EM, Sheffield VC and Alward WL: A family with Axenfeld-Rieger syndrome and peters anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene. Am J Ophthalmol. 135:368–75. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Berry FB, Lines MA, Oas JM, Footz T, Underhill DA, Gage PJ and Walter MA: Functional interactions between FOXC1 and PITX2 underlie the sensitivity to FOXC1 gene dose in Axenfeld-Rieger syndrome and anterior segment dysgenesis. Hum Mol Genet. 15:905–919. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Seifi M, Footz T, Taylor SA, Elhady GM, Abdalla EM and Walter MA: Novel PITX2 gene mutations in patients with Axenfeld-Rieger syndrome. Acta Ophthalmol. 94:e571–e579. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Berry FB, Mirzayans F and Walter MA: Regulation of FOXC1 stability and transcriptional activity by an epidermal growth factor-activated mitogen-activated protein kinase signaling cascade. J Biol Chem. 281:10098–10104. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Schachtschabel DO, Binninger EA and Rohen JW: In vitro cultures of trabecular meshwork cells of the human eye as a model system for the study of cellular aging. Arch Gerontol Geriatr. 9:251–262. 1989. View Article : Google Scholar : PubMed/NCBI

25 

Mandal AK and Pehere N: Early-onset glaucoma in Axenfeld-Rieger anomaly: Long-term surgical results and visual outcome. Eye (Lond). 30:936–942. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

September 2019
Volume 18 Issue 3

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Wu, X., Xie, H., Wu, T., Liu, W., Chen, L., Li, Z. ... Huang, H. (2019). A novel mutation of FOXC1 in a Chinese family with Axenfeld‑Rieger syndrome. Experimental and Therapeutic Medicine, 18, 2255-2261. https://doi.org/10.3892/etm.2019.7789
MLA
Wu, X., Xie, H., Wu, T., Liu, W., Chen, L., Li, Z., Wang, D., Wang, Y., Huang, H."A novel mutation of FOXC1 in a Chinese family with Axenfeld‑Rieger syndrome". Experimental and Therapeutic Medicine 18.3 (2019): 2255-2261.
Chicago
Wu, X., Xie, H., Wu, T., Liu, W., Chen, L., Li, Z., Wang, D., Wang, Y., Huang, H."A novel mutation of FOXC1 in a Chinese family with Axenfeld‑Rieger syndrome". Experimental and Therapeutic Medicine 18, no. 3 (2019): 2255-2261. https://doi.org/10.3892/etm.2019.7789