Lack of pathogenic mutations in SOS1 gene in phenytoin-induced gingival overgrowth patients.

Katia Margiotti, Giulia Pascolini, Federica Consoli, Valentina Guida, Carlo Di Bonaventura, Anna Teresa Giallonardo, Antonio Pizzuti, Alessandro De Luca

Journal: Archives of oral biology 2018;80():160-163

PMID: 28433619

Full Text on Elsevier Science View on PubMed

Abstract

OBJECTIVE

Gingival overgrowth is a side effect associated with some distinct classes of drugs, such as anticonvulsants, immunosuppressants, and calcium channel blockers. One of the main drugs associated with gingival overgrowth is the antiepileptic phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. It has been shown that mutation of human SOS1 gene is responsible for a rare hereditary gingival fibromatosis type 1, a benign gingival overgrowth. The aim of the present study is to evaluate the possible contribution of SOS1 mutation to gingival overgrowth-related phenotype.

DESIGN

We selected and screened for mutations a group of 24 epileptic patients who experienced significant gingival overgrowth following phenytoin therapy. Mutation scanning was carried out by denaturing high-performance liquid chromatography analysis of the entire coding region of the SOS1 gene. Novel identified variants were analyzed in-silico by using Alamut Visual mutation interpretation software, and comparison with normal control group was done.

RESULTS

Mutation scanning of the entire coding sequence of SOS1 gene identified seven intronic variants and one new exonic substitution (c.138G>A). The seven common intronic variants were not considered to be of pathogenic importance. The exonic substitution c.138G>A was found to be absent in 100 ethnically matched normal control chromosomes, but was not expected to have functional significance based on prediction bioinformatics tools.

CONCLUSIONS

This study represents the first mutation analysis of the SOS1 gene in phenytoin-induced gingival overgrowth epileptic patients. Present results suggest that obvious pathogenic mutations in the SOS1 gene do not represent a common mechanism underlying phenytoin-induced gingival overgrowth in epileptic patients; other mechanisms are likely to be involved in the pathogenesis of this drug-induced phenotype.

Address: Department of Experimental Medicine, Policlinico Umberto 1, Sapienza University of Rome, Rome, Italy; Laboratory of Molecular Medicine and Biotechnology, CIR, Campus Bio-Medico University of Rome, Italy. Electronic address: [email protected].; Department of Experimental Medicine, Policlinico Umberto 1, Sapienza University of Rome, Rome, Italy; Mendel Laboratory, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy. Electronic address: [email protected].; Mendel Laboratory, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy. Electronic address: [email protected].; Mendel Laboratory, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy. Electronic address: [email protected].; Department of Neuroscience, University of Rome "Sapienza", Rome, Italy. Electronic address: [email protected].; Department of Neuroscience, University of Rome "Sapienza", Rome, Italy. Electronic address: [email protected].; Department of Experimental Medicine, Policlinico Umberto 1, Sapienza University of Rome, Rome, Italy. Electronic address: [email protected].; Mendel Laboratory, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy. Electronic address: [email protected].

DOI: 10.1016/j.archoralbio.2017.04.002

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MeSH Terms: Adolescent, Adult, Anticonvulsants, Case-Control Studies, Chromatography, High Pressure Liquid, Epilepsy, Female, Gingival Overgrowth, Humans, Male, Middle Aged, Mutation, Phenytoin, SOS1 Protein