CASE REPORT article
Front. Med.
Sec. Dermatology
Case Report: PTCH1 splice-site mutation and sonidegib treatment in Gorlin-Goltz syndrome: clinical insights from a family case study
LINLI LIU
Heng Du
Neng Wang
Shuang Lv
Chunshui Yu
Lingli Deng
Suining Central Hospital, Suining, China
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Abstract
Gorlin-Goltz syndrome (nevoid basal cell carcinoma syndrome) is a rare autosomal dominant tumor-predisposition disorder characterized by multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, and variable systemic manifestations. Although pathogenic variants in PTCH1 are a major genetic cause, transcript-level functional evidence for splice-site variants and real-world data on tolerability-oriented dosing of Hedgehog pathway inhibitors remain limited. We report a three-generation family in which a heterozygous canonical PTCH1 splice-donor variant (NM_000264.5:c.3449+1G>A) segregated with disease. A minigene splicing assay demonstrated exon 20 skipping, supporting a loss-of-function mechanism. Two affected relatives with symptomatic BCC burden received oral sonidegib for 6 months using different schedules (200 mg once daily vs 200 mg every other day). Both patients showed clinical regression of target BCC lesions. Dysgeusia and alopecia occurred with daily dosing, whereas every-other-day dosing was well tolerated. This case highlights the value of transcript-level functional assays for interpreting PTCH1 splice-site variants and supports individualized, toxicity-guided sonidegib scheduling in selected patients with Gorlin-Goltz syndrome.
Summary
Keywords
basal cell carcinoma, Gorlin–Goltz syndrome, Hedgehog pathway inhibitor, minigene assay, Ptch1, Sonidegib, splice-site variant
Received
31 December 2025
Accepted
09 February 2026
Copyright
© 2026 LIU, Du, Wang, Lv, Yu and Deng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Lingli Deng
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