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

Abstract

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.