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Sofía Pérez Solórzano, Óscar Francisco Chacón-Camacho, Bertha Irene Fuerte-Flores, Daniel López-Moreno, Enriqueta Hofmann, Juan Carlos Zenteno-Ruíz; Identification Of Five Somatic Mutations In KRAS And FGFR1 Genes In Mexican Patients With Oculocutaneous Syndromes. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5398.
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RASopathies are a group of genetic syndromes caused by germinal mutations in genes coding for regulators of the RAS/MAPK pathway. The final effects of some of these mutations are so severe that patients can only survive in a mosaicism state limited to some affected cells and tissues.Whole genome sequencing has identified mutations in KRAS in patients with oculocutaneous síndromes like Oculoectodermic Syndrome (OMIM #600268) and Schimmelpenning-Feuerstein-Mims Syndrome (OMIM#163200) with different degrees of mosaicism.The aim of this work was to identify somatic mutations in RAS/GTPases and FGFR1 in seven Mexican patients with different oculocutaneous syndromes.
DNA was extracted from affected tissues with previous informed consent. Exons and flanking intronic regions of KRAS, NRAS, HRAS and FGFR1 were amplified by polymerase chain reaction (PCR). Direct sequencing was performed with the Big BigDye® Terminator Cycle Sequencing kit (Applied Biosystems, Foster City, CA). In silico analysis of identified variants was performed to confirm pathogenicity.
Seven patients were included in the study. Two had epidermoid cyst alone and five had a clinical diagnosis of an oculocutaneous syndrome. Five different mutations were identified. Patients with a syndromic presentation were the ones with a mutation while patients with only epidermoid cyst had none. Pathogenic variants found in these patients confirmed a somatic mosaicism.
Mutations that activate the GTPases RAS in somatic mosaicism have been identified in patients with oculocutaneous syndromes. We found four different mutations in KRAS and one in FGFR1 in Mexican patients from different affected tissues demonstrating mosaicism in these syndromes. Molecular study allows the understanding of the molecular-pathogenic mechanisms for prevention and treatment in these patients.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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