Case Report: PTCH1 splice-site mutation and sonidegib treatment in Gorlin-Goltz syndrome: clinical insights from a family case study

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Source: Frontiers Medicine

Original: https://www.frontiersin.org/articles/10.3389/fmed.2026.1778460...

Published: 2026-02-24T00:00:00Z

Gorlin-Goltz syndrome is a rare autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, and other systemic manifestations. In a three-generation family, a heterozygous PTCH1 splice site mutation (NM000264.5:c.3449 + 1G > A) was inherited with the disease. A minigene splicing assay demonstrated skipping of exon 20, leading to loss of gene function. Two patients with multiple BCCs received sonidegib orally for 6 months: one 200 mg daily, the other 200 mg every other day. Both showed clinical regression of BCC lesions. Dysgeusia and alopecia occurred with daily dosing, while every-other-day dosing was well tolerated. The case confirms the importance of transcript-level functional assays for PTCH1 variants and supports individualized dosing of sonidegib according to toxicity.