TY - JOUR
T1 - Novel rare frameshift variation in aggressive periodontitis
T2 - Exomic and familial-screening analysis
AU - Taiete, Tiago
AU - Casati, Marcio Z.
AU - Martins, Luciane
AU - Andia, Denise C.
AU - Mofatto, Luciana S.
AU - Coletta, Ricardo D.
AU - Monteiro, Mabelle F.
AU - Araújo, Cássia F.
AU - Santamaria, Mauro P.
AU - Nociti, Francisco H.
AU - Corrêa, Mônica G.
AU - Sallum, Enilson A.
AU - Casarin, Renato C.
N1 - Publisher Copyright:
© John Wiley and Sons Inc. All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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 EEF-SEC (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.
AB - 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 EEF-SEC (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.
KW - genetic association studies
KW - genetic markers
KW - genetic variation
KW - genotype
KW - periodontal diseases
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U2 - 10.1002/JPER.19-0182
DO - 10.1002/JPER.19-0182
M3 - Article
C2 - 31373687
AN - SCOPUS:85079563918
SN - 0022-3492
VL - 91
SP - 263
EP - 273
JO - Journal of Periodontology
JF - Journal of Periodontology
IS - 2
ER -