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Novel rare frameshift variation in aggressive periodontitis: Exomic and familial‐screening analysis
Author(s) -
Taiete Tiago,
Casati Marcio Z.,
Martins Luciane,
Andia Denise C.,
Mofatto Luciana S.,
Coletta Ricardo D.,
Monteiro Mabelle F.,
Araújo Cássia F.,
Santamaria Mauro P.,
Corrêa Mônica G.,
Sallum Enilson A.,
Nociti Francisco H.,
Casarin Renato C.
Publication year - 2020
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1002/jper.19-0182
Subject(s) - frameshift mutation , proband , in silico , indel , genetics , biology , exome sequencing , genetic variation , missense mutation , single nucleotide polymorphism , gene , genotype , mutation
Abstract Background Aggressive periodontitis (AgP), currently periodontitis grade C, presents early onset, rapid progression, and a poorly established genetic association. Thus, this study aimed to identify genetic variants associated with AgP via whole exome sequencing (WES) through a familial screening approach. Methods WES was performed in two nuclear families, including a proband and a parent affected by AgP and an unaffected parent and sibling. Common variants among affected individuals, excluding those common to healthy people, from each family, composed the data set associated with AgP. In silico analysis evaluated the impact of each variant on protein structure and protein‐protein interactions. Moreover, identified deleterious variants were validated in a populational analysis ( n = 96). Results The missense single nucleotide variations (SNVs) rs142548867 in EEFSEC (c.668C>T), rs574301770 in ZNF136 (c.466C>G), and rs72821893 in KRT25 (c.800G>A) and the frameshift indels rs37146475 in GPRC6A (c.2323‐2324insT) and c.1366_1372insGGAGCAG in ELN were identified in AgP and have a predicted functional impact on proteins. In silico analysis indicated that the indel in GPRC6A generates a loss of the C‐terminal tail of the Gprca protein. Furthermore, this SNV was significantly associated with AgP in a population‐based investigation. Conclusion Novel frameshift variation in GPRC6A (c.2323‐2324insT) was identified as a potential genetic alteration associated with AgP occurrence.