Citation:Moon S,Kim N,Lee J.Clinical and genetic analysis of Ser341Pro MYOC variant in a Korean family with primary open angle glaucoma.Int J Ophthalmol 2020;13(11):1689-1696,doi:10.18240/ijo.2020.11.02
Clinical and genetic analysis of Ser341Pro MYOC variant in a Korean family with primary open angle glaucoma
Received:January 13, 2020  Revised:July 29, 2020
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DOI:10.18240/ijo.2020.11.02
Key Words:Ser341Pro variant  primary open angle glaucoma  Korean
Fund Project:Supported by Patient-Centered Clinical Research Coordinating Center funded by the Ministry of Health & Welfare, Republic of Korea (No.HI19C0481; No.HC19C0276).
        
AuthorInstitution
Sangwoo Moon Department of Ophthalmology, Pusan National University College of Medicine, Busan 49241, Republic of Korea; Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
Namhee Kim Department of Laboratory Medicine, Dong A University College of Medicine, Busan 49201, Republic of Korea
Jiwoong Lee Department of Ophthalmology, Pusan National University College of Medicine, Busan 49241, Republic of Korea; Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
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Abstract:
      AIM: To report the first discovery of Ser341Pro myocilin (MYOC) variant in Korea and analyze its clinical characteristics and genetic significance.

    METHODS: Ten family members from three generations participated in this study and received the thorough ophthalmologic examination. Focused exome sequencing on a proband was performed to confirm the target mutations (MYOC c.1021T>C) in the family members, and the direct sequencing was conducted. Variant was analyzed according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines.

    RESULTS: A nucleotide change from thymine to cytosine at c.1021T>C was found in eight family members. Three members diagnosed with primary open angle glaucoma (POAG) were characterized by severe clinical presentations, high intraocular pressure, and poor response to medical treatment (100% of the patient required filtering surgery). On variant analysis by ACMG/AMP guidelines, Ser341Pro is not found in normal population. Multiple computational predictive programs support a deleterious effect of Ser341Pro variant (PolyPhen 2, SIFT, Mutation Taster). Ser341Pro could be involved in moderate (PM) and supporting (PP) criteria (PM1, PM2, PP2, PP3). Combining the criteria, Ser341Pro has a combination of 2 moderate (PM1+PM2) and 2 supporting (PP2+PP3) criteria, which is interpreted to “likely pathogenic”.

    CONCLUSION: The Ser341Pro variant is correlated with severe phenotype of POAG. There are similar clinical aspects to previous studies: autosomal dominant inheritance, incomplete penetrance (62.50% and 66.67%), and proportion of patients requiring trabeculectomy (100% in both study). According to ACMG/AMP guidelines and the previous basic researches, the Ser341Pro variant had a “strong evidence of pathogenicity (PS3)” and then it could be interpreted to “pathogenic (PS3, PM1, PM2, PP2, PP3)”. Additionally, Ser341Pro variant can be reported as “c.1021T>C (p.Ser341Pro), likely pathogenic, POAG, autosomal dominant” according to guideline.

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