Lack of pathogenic mutations in SOS1 gene in phenytoin-induced gingival overgrowth patients |
| |
| Affiliation: | 1. Department of Experimental Medicine, Policlinico Umberto 1, Sapienza University of Rome, Rome, Italy;2. Laboratory of Molecular Medicine and Biotechnology, CIR, Campus Bio-Medico University of Rome, Italy;3. Mendel Laboratory, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy;4. Department of Neuroscience, University of Rome “Sapienza”, Rome, Italy;1. School of Natural Sciences, Griffith University, Nathan, Qld 4111, Australia;2. Eskitis Institute for Drug Discovery, Griffith University, Nathan, Qld 4111, Australia;1. Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, China;2. Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, China;3. Iron Metabolism Laboratory, Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, QLD, Australia;4. Vita-Salute University and Istituto Di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan, Italy;5. Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;6. Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, China;1. Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong 518060, China;2. Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, China;3. Department of Chest Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518000, China;4. Department of Pediatrics, University of Illinois at Chicago, Chicago, IL 60612, USA |
| |
| Abstract: | ObjectiveGingival 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.DesignWe 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.ResultsMutation 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.ConclusionsThis 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. |
| |
| Keywords: | Gingival overgrowth Phenytoin Hereditary gingival fibromatosis type 1 |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
