• Genetic Variants in the TBC1D2B Gene Are Associated with Ramon Syndrome and Hereditary Gingival Fibromatosis

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06/12/2024 by   

Metadata

Document Title

Genetic Variants in the TBC1D2B Gene Are Associated with Ramon Syndrome and Hereditary Gingival Fibromatosis

Author

Kularbkaew T., Thongmak T., Sandeth P., Durward C.S., Vittayakittipong P., Duke P., Iamaroon A., Kintarak S., Intachai W., Ngamphiw C., Tongsima S., Jatooratthawichot P., Cox T.C., Ketudat Cairns J.R., Kantaputra P.

Affiliations

Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand; Division of Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand; Pediatric Division, Hatyai Hospital, Songkhla, 90110, Thailand; Department of Oral and Maxillofacial Surgery, Preah Ang Duong Hospital, Phnom Penh 120201, Cambodia; Faculty of Dentistry, University of Puthisastra, Phnom Penh 120201, Cambodia; Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Prince of Songkla University, Songkhla, 90110, Thailand; Royal Adelaide Hospital, Adelaide, SA 5000, Australia; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand; Department of Oral Diagnostic Sciences, Faculty of Dentistry, Prince of Songkla University, Songkhla, 90110, Thailand; National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, Thailand Science Park, Pathum Thani, 12120, Thailand; School of Chemistry, Institute of Science, Center for Biomolecular Structure, Function and Application, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand; Departments of Oral & Craniofacial Sciences, School of Dentistry, and Pediatrics, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, United States

Source Title

International Journal of Molecular Sciences

ISSN

16616596

Year

2024

Volume

25

Issue

16

Open Access

All Open Access, Gold

Publisher

Multidisciplinary Digital Publishing Institute (MDPI)

DOI

10.3390/ijms25168867

Abstract

Ramon syndrome (MIM 266270) is an extremely rare genetic syndrome, characterized by gingival fibromatosis, cherubism-like lesions, epilepsy, intellectual disability, hypertrichosis, short stature, juvenile rheumatoid arthritis, and ocular abnormalities. Hereditary or non-syndromic gingival fibromatosis (HGF) is also rare and considered to represent a heterogeneous group of disorders characterized by benign, slowly progressive, non-inflammatory gingival overgrowth. To date, two genes, ELMO2 and TBC1D2B, have been linked to Ramon syndrome. The objective of this study was to further investigate the genetic variants associated with Ramon syndrome as well as HGF. Clinical, radiographic, histological, and immunohistochemical examinations were performed on affected individuals. Exome sequencing identified rare variants in TBC1D2B in both conditions: a novel homozygous variant (c.1879_1880del, p.Glu627LysfsTer61) in a Thai patient with Ramon syndrome and a rare heterozygous variant (c.2471A>G, p.Tyr824Cys) in a Cambodian family with HGF. A novel variant (c.892C>T, p.Arg298Cys) in KREMEN2 was also identified in the individuals with HGF. With support from mutant protein modeling, our data suggest that TBC1D2B variants contribute to both Ramon syndrome and HGF, although variants in additional genes might also contribute to the pathogenesis of HGF. © 2024 by the authors.

License

CC BY

Rights

Authors

Publication Source

Scopus

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