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Title: | Oculocutaneous albinism type 1B associated with a functionally significant tyrosinase gene polymorphism detected with Whole Exome Sequencing | Authors: | Mendez, Rodrigo Iqbal, Sumaiya Vishnopolska, Sebastián A Martínez, Cinthia Dibner, Glenda Aliano, Rocio Zaiat, Jonathan Biagioli, Germán Fernandez, Cecilia Turjanski, Adrián G Campbell, Arthur J Mercado, Graciela Marti, Marcelo A |
Keywords: | Tirosina Fenol-Liasa;Secuenciación del Exoma Completo | Issue Date: | Jun-2021 | Journal: | Ophthalmic genetics | Abstract: | Background: Oculocutaneous albinism (OCA) is a Mendelian disorder characterized by hypopigmentation of the skin, hair, and eyes, hypoplastic fovea, and low vision, known to be caused by mutations in the Tyrosinase (TYR) gene. Among the known TYR variants, some reduce but do not completely eliminate tyrosinase activity, allowing residual production of melanin and resulting in a contradictory assignment as either pathogenic or benign, preventing a precise clinical diagnostic.Materials and Methods: In the present work, we performed Whole Exome Sequencing and subsequent Sanger sequencing in a young male clinically diagnosed with OCA.Results: Whole-exome sequencing analysis revealed the identification of two variants in trans in TYR. The first, corresponds to a known pathogenic variant G47D, while the second S192Y, was considered a polymorphism due to its relatively high frequency in the European population.Conclusion: The lack of other pathogenic variants in TYR, the reported reduced enzymatic activity (ca. 40% respect to wt) for S192Y, together with the structural in-silico analysis strongly suggest that both reported variants are jointly disease-causing and that S192Y should be considered as likely pathogenic, especially when it is found in trans with a null variant. |
Description: | Fil: Mendez, Rodrigo. ANLIS Dr. C. G. Malbrán. Centro Nacional de Genética Médica (CeNaGeM). Departamento de medicina genética; Argentina Fil: Iqbal, Sumaiya. Center for Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts; United States Fil: Vishnopolska, Sebastián. Universidad de Buenos Aires; Buenos Aires, Argentina Fil: Martinez, Cinthia. Centro Nacional de Genética Médica "Dr. Eduardo E. Castilla", ANLIS; Buenos Aires, Argentina Fil: Dibner, Glenda. Departamento de Oftalmología, Hospital Rivadavia; Buenos Aires, Argentina Fil: Aliano, Rocio. Departamento de Oftalmología, Hospital Rivadavia; Buenos Aires, Argentina Fil: Zaiat, Jonathan. Departamento de Química Biológica, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) CONICET; Buenos Aires, Argentina Fil: Biagioli, Germán. Universidad de Buenos Aires; Buenos Aires, Argentina Fil: Fernandez, Cecilia. Laboratorio de Genética, Novagen; Buenos Aires, Argentina Fil: Turjanski, Adrian. Departamento de Química Biológica, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) CONICET; Buenos Aires, Argenina Fil: Campbell, Arthur J. Center for Development of Therapeutics, Broad Institute of MIT and Harvard; United States Fil: Mercado, Graciela. Centro Nacional de Genética Médica "Dr. Eduardo E. Castilla", ANLIS; Buenos Aires, Argentina Fil: Marti, Marcelo A. Universidad de Buenos Aires; Buenos Aires, Argentina |
URI: | http://sgc.anlis.gob.ar/handle/123456789/2482 | DOI: | 10.1080/13816810.2021.1888129 |
Appears in Collections: | Artículos |
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