Genetic analysis of hereditary gingival fibromatosis using whole exome sequencing and bioinformatics.
OBJECTIVE
Our study aims to identify genetic variants associated with hereditary gingival fibromatosis (HGF) by applying whole-exome sequencing (WES) and bioinformatics analyses such as gene set enrichment analysis (GSEA) and protein functional network study.


METHODS
Two affected siblings whose grandparents and parents have normal gingiva were chosen for our investigation. Saliva collected from the patients and their parents were used for WES. GSEA and protein functional network study were performed to find gene groups in a biological coordination which are associated with HGF.


RESULTS
Genetic variants for homozygotes and compound heterozygotes were analyzed and translated into 845 genes. The result from protein functional network study showed that these genetic variants were mainly observed in genes affecting fibronectin as well as the immune and autoimmune system. Additionally, three mutated genes in our HGF patients, TMCO1, RIN2, and INSR, were found through human phenotype ontology (HPO) to have potential to contribute to gingival hyperplasia.


CONCLUSIONS
Genetic analysis of HGF in this study implicated mutations in fibronectin and the immune system as triggering abnormal gingival fibromatosis.
Department of IT Convergence and Engineering, Pohang University of Science and Technology, Pohang, Korea.
J
J
Hwang
Department of Prosthodontics, College of Dentistry, Yonsei University, Seoul, Korea.
Y-L
YL
Kim
Department of Prosthodontics, College of Dentistry, Yonsei University, Seoul, Korea.
S
S
Kang
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
S
S
Kim
Department of Pediatric Dentistry, College of Dentistry, Yonsei University, Seoul, Korea.
S-O
SO
Kim
Department of Prosthodontics, College of Dentistry, Yonsei University, Seoul, Korea.
J H
JH
Lee
Department of Prosthodontics, College of Dentistry, Yonsei University, Seoul, Korea.
D-H
DH
Han
D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics; D015220:Calcium Channels; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D059472:Exome / Q000235:genetics*; D005260:Female; D005351:Fibromatosis, Gingival / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D016678:Genome / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010375:Pedigree; D011972:Receptor, Insulin / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D015703:Antigens, CD; D015220:Calcium Channels; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; C447829:RIN2 protein, human; C575495:TMCO1 protein, human; C435941:INSR protein, human; D011972:Receptor, Insulin
bioinformatics; fibronectin; gingival hyperplasia; hereditary gingival fibromatosis; whole-exome sequencing