Identification of Novel Nonsense RPGR Variant Causing Mild X-Linked Cone-Rod Dystrophy and Myopia  

作　　者：Kunka Kamenarova Sylvia Cherninkova Kalina Mihova Rosen Georgiev Yana Nikolaeva Radka Kaneva Kunka Kamenarova;Sylvia Cherninkova;Kalina Mihova;Rosen Georgiev;Yana Nikolaeva;Radka Kaneva(Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University—Sofia, Sofia, Bulgaria;Laboratory of Genomic Diagnostics, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University—Sofia, Sofia, Bulgaria;Clinic of Nervous diseases, University Hospital “Alexandrovska”, Sofia, Bulgaria;Clinic of Eye Diseases, University Hospital “Alexandrovska”, Sofia, Bulgaria;Eye Clinic “Vision”, Sofia, Bulgaria)

机构地区：[1]Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University—Sofia, Sofia, Bulgaria [2]Laboratory of Genomic Diagnostics, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University—Sofia, Sofia, Bulgaria [3]Clinic of Nervous diseases, University Hospital “Alexandrovska”, Sofia, Bulgaria [4]Clinic of Eye Diseases, University Hospital “Alexandrovska”, Sofia, Bulgaria [5]Eye Clinic “Vision”, Sofia, Bulgaria

出　　处：《Case Reports in Clinical Medicine》2022年第10期422-434,共13页临床医学病理报告（英文）

摘　　要：Background: Mutations in the RPGR gene are associated with rod-cone or cone-rod dystrophy, the latter associated with mutations at the distal end. Cone-rod dystrophy (CRD) is a subgroup of hereditary retinal disorders characterized by the primary degeneration of cone photoreceptors often followed by progressive loss of rod photoreceptors in the peripheral visual field. Purpose: The aim of this study was to describe the milder CRD phenotype associated with a novel pathogenic variant c.1905 + 223C > T (p.Q710X) found in RPGR which results in shortening of the photoreceptor specific isoform RPGR ^ORF15. Method: An 11-year-old boy with symptoms of CRD and two female relatives were referred for detailed ophthalmic examinations. Genetic testing was performed by next-generation sequencing of clinical exome followed by Sanger sequencing for segregation analysis. Results: Genetic analysis identified a novel variant in ORF15 of the RPGR gene (c.1905 + 223C > T, p.Q710X) in the proband considered as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) standards. Segregation study identified the mutation in a heterozygous state in the mother and her sister. Detailed ophthalmological examination revealed slightly reduced color vision and scattered grayish point-like deposits in the posterior pole of the fundus in the male patient. All mutation carriers were myopic. Conclusion: We report a novel pathogenic RPGR variant in a Bulgarian patient with clinical features compatible with the CRD diagnosis. This condition is inherited as an X-linked dominant trait in its familial form presenting with a mild CRD phenotype in the male hemizygous proband and a moderate to high myopia in the female heterozygous carriers.Background: Mutations in the RPGR gene are associated with rod-cone or cone-rod dystrophy, the latter associated with mutations at the distal end. Cone-rod dystrophy (CRD) is a subgroup of hereditary retinal disorders characterized by the primary degeneration of cone photoreceptors often followed by progressive loss of rod photoreceptors in the peripheral visual field. Purpose: The aim of this study was to describe the milder CRD phenotype associated with a novel pathogenic variant c.1905 + 223C > T (p.Q710X) found in RPGR which results in shortening of the photoreceptor specific isoform RPGR ^ORF15. Method: An 11-year-old boy with symptoms of CRD and two female relatives were referred for detailed ophthalmic examinations. Genetic testing was performed by next-generation sequencing of clinical exome followed by Sanger sequencing for segregation analysis. Results: Genetic analysis identified a novel variant in ORF15 of the RPGR gene (c.1905 + 223C > T, p.Q710X) in the proband considered as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) standards. Segregation study identified the mutation in a heterozygous state in the mother and her sister. Detailed ophthalmological examination revealed slightly reduced color vision and scattered grayish point-like deposits in the posterior pole of the fundus in the male patient. All mutation carriers were myopic. Conclusion: We report a novel pathogenic RPGR variant in a Bulgarian patient with clinical features compatible with the CRD diagnosis. This condition is inherited as an X-linked dominant trait in its familial form presenting with a mild CRD phenotype in the male hemizygous proband and a moderate to high myopia in the female heterozygous carriers.

关 键 词：Cone-Rod Dystrophy MYOPIA RPGR Novel Mutation 

分 类 号：R73[医药卫生—肿瘤]