Case Report| Volume 135, ISSUE 3, e68-e73, March 2023

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A new TRPV4 mutation in a case of multiple central giant cell granulomas of the jaws

Published:October 20, 2022DOI:
      Sporadic central giant cell granulomas of the jaws (GCGJ) are often solitary lesions, characterized by KRAS, FGFR1, and TRPV4 somatic mutations. Multifocal lesions may occur and are associated with hyperparathyroidism or underlying syndromes such as cherubism, which is marked by SH3BP2 mutations, and RASopathies, which are caused by mutations in the FGFR-RAS-RAF-MEK-ERK signaling cascade. The diagnosis of multiple GCGJ can be challenging. The present case reports a 14-year-old boy with multiple central GCGJ and no obvious syndromic trait. Sanger sequencing-based analysis revealed wild-type sequences for SH3BP2 (exon 9), KRAS (exons 2-4), and FGFR1 (exons 9 and 10) genes. A rare TRPV4 somatic mutation (p.Val708Met) was detected in the lesion on the right side of the mandible, whereas the other tumor and the normal oral mucosa revealed wild-type TRPV4 sequences. This report expands the spectrum of TRPV4 somatic mutations in central GCGJ.
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        • Schreuder WH
        • van der Wal JE
        • de Lange J
        • van den Berg H.
        Multiple versus solitary giant cell lesions of the jaw: similar or distinct entities?.
        Bone. 2021; 149115935
        • Ueki Y
        • Tiziani V
        • Santanna C
        • et al.
        Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism.
        Nat Genet. 2001; 28: 125-126
        • Chrcanovic BR
        • Guimarães LM
        • Gomes CC
        • Gomez RS.
        Cherubism: a systematic literature review of clinical and molecular aspects.
        Int J Oral Maxillofac Surg. 2021; 50: 43-53
        • Gomes CC
        • Gayden T
        • Bajic A
        • et al.
        TRPV4 and KRAS and FGFR1 gain-of-function mutations drive giant cell lesions of the jaw.
        Nat Commun. 2018; 9: 4572
        • Gomes CC
        • Diniz MG
        • Bastos VC
        • Bernardes VF
        • Gomez RS.
        Making sense of giant cell lesions of the jaws (GCLJ): lessons learned from next-generation sequencing.
        J Pathol. 2020; 250: 126-133
        • Carvalho VM
        • Perdigão PF
        • Pimenta FJ
        • de Souza PE
        • Gomez RS
        • De Marco L.
        A novel mutation of the SH3BP2 gene in an aggressive case of cherubism.
        Oral Oncol. 2008; 44: 153-155
        • Carvalho VM
        • Perdigao PF
        • Amaral FR
        • de Souza PE
        • De Marco L
        • Gomez RS.
        Novel mutations in the SH3BP2 gene associated with sporadic central giant cell lesions and cherubism.
        Oral Dis. 2009; 15: 106-110
        • Nilius B
        • Voets T.
        The puzzle of TRPV4 channelopathies.
        EMBO Rep. 2013; 14: 152-163
        • Ragamin A
        • Gomes CC
        • Bindels-de Heus K
        • et al.
        De novo TRPV4 Leu619Pro variant causes a new channelopathy characterised by giant cell lesions of the jaws and skull, skeletal abnormalities and polyneuropathy.
        J Med Genet. 2022; 59: 305-312
        • Taga A
        • Peyton MA
        • Goretzki B
        • et al.
        TRPV4 mutations causing mixed neuropathy and skeletal phenotypes result in severe gain of function.
        Ann Clin Transl Neurol. 2022; 9: 375-391
        • Deng Z
        • Paknejad N
        • Maksaev G
        • et al.
        Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms.
        Nat Struct Mol Biol. 2018; 25: 252-260
        • Everaerts W
        • Zhen X
        • Ghosh D
        • et al.
        Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis.
        Proc Natl Acad Sci U S A. 2010; 107: 19084-19089
        • Goyal N
        • Skrdla P
        • Schroyer R
        • et al.
        Clinical pharmacokinetics, safety, and tolerability of a novel, first-in-class TRPV4 ion channel inhibitor, GSK2798745, in healthy and heart failure subjects.
        Am J Cardiovasc Drugs. 2019; 19: 335-342