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Abstract #81332 Published in IGR 20-3
Compound heterozygous mutations in gene leads to severe primary congenital glaucoma phenotype
Song N; Leng L; Yang XJ; Zhang YQ; Tang C; Chen WS; Zhu W; Yang XInternational Journal of Ophthalmology 2019; 12: 909-914
AIM: To identify the novel mutation alleles in the gene of primary congenital glaucoma (PCG) patients at Shandong Province of China, and investigate their correlation with glaucomatous features. METHODS: The DNA from the peripheral blood of 13 congenital glaucoma patients and 50 ethnically matched healthy controls from the affiliated hospital of Qingdao University were extracted. The coding region of the gene was amplified by PCR and direct DNA sequencing was performed. Disease causing-variants were analyzed by comparing the sequences and the structures of wild type and mutant proteins by PyMOL software. RESULTS: Two missense mutations, including A330F caused by c.988G>T&c.989C>T, and R390H caused by c.1169G>A, were identified in one of the 13 PCG patients analyzed in our study. A330F mutation was observed to be novel in the Chinese Han population, which dramatically altered the protein structure of gene, including the changes in the ligand-binding pocket. Furthermore, R390H mutation caused the changes in heme-protein binding site of this gene. In addition, the clinical phenotype displayed by PCG patient with these mutations was more pronounced than other PCG patients without these mutations. Multiple surgeries and combined drug treatment were not effective in reducing the elevated intraocular pressure in this patient. CONCLUSION: A novel A330F mutation is identified in the gene of Chinese PCG patient. Moreover, in combination with other mutation R390H, this PCG patient shows significant difference in the protein structure, which may specifically contribute to severe glaucomatous phenotype.
Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China.
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