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Mutation Survey of Candidate Genes and Genotype-Phenotype Analysis in 20 Southeastern Chinese Patients with Axenfeld-Rieger Syndrome.
Curr Eye Res. 2018 11; 43(11):1334-1341.CE

Abstract

Purpose/aim of the study: To conduct a survey spectrum of the PITX2, FOXC1, and PRDM5 genes to reveal genotype-phenotype correlations in a cohort of Southeastern Chinese patients with Axenfeld-Rieger syndrome (ARS).

MATERIALS AND METHODS

A total of 20 probands with ARS were recruited in Southeast China. All patients underwent full ocular and systemic examinations. Sanger sequencing was used to analyze all coding regions of and regions adjacent to PITX2, FOXC1, and PRDM5 and 13 upstream regulatory elements of PITX2. Multiplex ligation-dependent probe amplification was performed to detect gross insertions and deletions in PITX2 and FOXC1. Quantitative polymerase chain reaction was used to detect copy number variations in regulatory elements of PITX2. A bioinformatics analysis was conducted to evaluate the pathogenicity of variants.

RESULTS

Eleven mutations, including eight novel mutations, were identified in PITX2. Seven of the mutations were truncations. A genotype-phenotype correlation analysis showed that 81.8% (9/11) of patients with mutations in PITX2 developed glaucoma before reaching 10 years old. The proportion of patients without detected mutations was only 33.3% (3/9, P = 0.0399). In patient G1399, ultrasound biomicroscopy revealed that the left eye exhibited a phenotype similar to aniridia with complete angle closure and a remaining stub of iris tissue.

CONCLUSION

This is the first genetic study of a cohort of Southeastern Chinese patients with ARS. Eight novel mutations were detected, expanding the mutation spectrum of PITX2. PITX2 may be a major candidate gene for ARS in Southeastern Chinese patients. Truncations may be the primary mutation type in PITX2. Glaucoma onset may be earlier in patients with mutations in PITX2 than in those without mutations in PITX2 and FOXC1. A block of the anterior chamber angle by the end of the iris might represent the main factor influencing the development of glaucoma in ARS patients with an asymmetric aniridia phenotype.

Authors+Show Affiliations

a State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center , Sun Yat-Sen University , Guangzhou , China.a State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center , Sun Yat-Sen University , Guangzhou , China.a State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center , Sun Yat-Sen University , Guangzhou , China.a State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center , Sun Yat-Sen University , Guangzhou , China.a State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center , Sun Yat-Sen University , Guangzhou , China.a State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center , Sun Yat-Sen University , Guangzhou , China.a State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center , Sun Yat-Sen University , Guangzhou , China.a State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center , Sun Yat-Sen University , Guangzhou , China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29939776

Citation

Wang, Xun, et al. "Mutation Survey of Candidate Genes and Genotype-Phenotype Analysis in 20 Southeastern Chinese Patients With Axenfeld-Rieger Syndrome." Current Eye Research, vol. 43, no. 11, 2018, pp. 1334-1341.
Wang X, Liu X, Huang L, et al. Mutation Survey of Candidate Genes and Genotype-Phenotype Analysis in 20 Southeastern Chinese Patients with Axenfeld-Rieger Syndrome. Curr Eye Res. 2018;43(11):1334-1341.
Wang, X., Liu, X., Huang, L., Fang, S., Jia, X., Xiao, X., Li, S., & Guo, X. (2018). Mutation Survey of Candidate Genes and Genotype-Phenotype Analysis in 20 Southeastern Chinese Patients with Axenfeld-Rieger Syndrome. Current Eye Research, 43(11), 1334-1341. https://doi.org/10.1080/02713683.2018.1493129
Wang X, et al. Mutation Survey of Candidate Genes and Genotype-Phenotype Analysis in 20 Southeastern Chinese Patients With Axenfeld-Rieger Syndrome. Curr Eye Res. 2018;43(11):1334-1341. PubMed PMID: 29939776.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutation Survey of Candidate Genes and Genotype-Phenotype Analysis in 20 Southeastern Chinese Patients with Axenfeld-Rieger Syndrome. AU - Wang,Xun, AU - Liu,Xing, AU - Huang,Liqin, AU - Fang,Shaohua, AU - Jia,Xiaoyun, AU - Xiao,Xueshan, AU - Li,Shiqiang, AU - Guo,Xiangming, Y1 - 2018/07/17/ PY - 2018/6/26/pubmed PY - 2019/10/19/medline PY - 2018/6/26/entrez KW - Axenfeld–Rieger syndrome KW - PITX2 KW - Southeastern Chinese population KW - asymmetric phenotype KW - glaucoma SP - 1334 EP - 1341 JF - Current eye research JO - Curr Eye Res VL - 43 IS - 11 N2 - : Purpose/aim of the study: To conduct a survey spectrum of the PITX2, FOXC1, and PRDM5 genes to reveal genotype-phenotype correlations in a cohort of Southeastern Chinese patients with Axenfeld-Rieger syndrome (ARS). MATERIALS AND METHODS: A total of 20 probands with ARS were recruited in Southeast China. All patients underwent full ocular and systemic examinations. Sanger sequencing was used to analyze all coding regions of and regions adjacent to PITX2, FOXC1, and PRDM5 and 13 upstream regulatory elements of PITX2. Multiplex ligation-dependent probe amplification was performed to detect gross insertions and deletions in PITX2 and FOXC1. Quantitative polymerase chain reaction was used to detect copy number variations in regulatory elements of PITX2. A bioinformatics analysis was conducted to evaluate the pathogenicity of variants. RESULTS: Eleven mutations, including eight novel mutations, were identified in PITX2. Seven of the mutations were truncations. A genotype-phenotype correlation analysis showed that 81.8% (9/11) of patients with mutations in PITX2 developed glaucoma before reaching 10 years old. The proportion of patients without detected mutations was only 33.3% (3/9, P = 0.0399). In patient G1399, ultrasound biomicroscopy revealed that the left eye exhibited a phenotype similar to aniridia with complete angle closure and a remaining stub of iris tissue. CONCLUSION: This is the first genetic study of a cohort of Southeastern Chinese patients with ARS. Eight novel mutations were detected, expanding the mutation spectrum of PITX2. PITX2 may be a major candidate gene for ARS in Southeastern Chinese patients. Truncations may be the primary mutation type in PITX2. Glaucoma onset may be earlier in patients with mutations in PITX2 than in those without mutations in PITX2 and FOXC1. A block of the anterior chamber angle by the end of the iris might represent the main factor influencing the development of glaucoma in ARS patients with an asymmetric aniridia phenotype. SN - 1460-2202 UR - https://www.unboundmedicine.com/medline/citation/29939776/Mutation_Survey_of_Candidate_Genes_and_Genotype_Phenotype_Analysis_in_20_Southeastern_Chinese_Patients_with_Axenfeld_Rieger_Syndrome_ DB - PRIME DP - Unbound Medicine ER -