The Molar-Incisor Hypomineralization (MIH) is a development enamel defect that shows an idiopathic origin, and affects one or more permanent first molars and can be associated with permanent incisors. From etiological aspect, it can be considered a multifactorial and complex condition. Recently, MIH has associated with enamel formation related genes, and although it has a well-established genetic component, studies with more comprehensive methodologies are needed in order to elucidate which variations are necessary for the development of this condition. However, considering that the human genome contains thousands of genetic variants (mutations and polymorphisms), the genetic etiology of HMI needs to be investigated in a broader way. The aim of this study is to identify genetic alterations, through the investigation of the whole exoma sequencing in patients with MIH in order to better understand the genetic component as the etiological factor of this condition. The whole exome sequencing is also known as New Generation Sequencing (NGS), which is the most modern genetic screening methodology. Since 2008 we have organized a database of DNA samples from 101 families that have at least one child affected by MIH. Each patient has information regarding to medical history, dental characteristics, and retrospective information from the gestational period of the affected children. Saliva samples were collected from 295 patients (of 101 families), whose DNA was extracted and quantified. An aliquot of this DNA will be used for extensive investigation of genetic variants through whole exome sequencing, which will be performed by an outsourced and specialized company. As soon as the files containing the thousands of sequences are made available, we will perform the complex bioinformatics and statistical analyzes. Initially, we will compare the sequencing among members of each family by discarding the common variants between the affected parent and the unaffected parent, as well as the common variants with the unaffected child. It will be selected only the common variants among affected parents and the affected children. The same variant filtering methodology will be applied for each family, until the sequences of the affected individuals are compared, trying to identify the common variants among them that can be considered as associated with the MIH. The selected variants will be validated by Sanger sequencing. To investigate the function of the validated variants, Bioinformatics analyzes will be performed as a construction of protein-protein interaction network (PPI) and in silico evaluations to identify the impact of each variant on the protein structure of the respective gene. Finally, we intend to correlate such genetic variants with the clinical characteristics of the patients and the severity of the MIH.
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