A Novel Case of Gorlin Syndrome Mosaicism Involving an SMO Gene Mutation: Clinical, Histological and Molecular Analysis of Basaloid Tumours.

Gorlin syndrome comprises multiple basal cell carcinomas (BCCs), basal cell naevi (BCNs), odontogenic keratocysts, skeletal abnormalities and other features (1). Identification of the PTCH1 gene as the candidate gene for Gorlin syndrome demonstrated that activation of the Hedgehog (Hh) pathway is the key driver in the physiology and pathology of BCC formation (2). Gorlin syndrome has been linked to germline mutations of various members of the Hh pathway, including mainly PTCH1 and also PTCH2 and SUFU; however, to date, SMO germline mutations have not been described. Recently, a case of Gorlin syndrome type 1 mosaicism presented a somatic mutation of SMO L412F (3). This mutation has been described as oncogenic, conferring constitutive activation of the Hh pathway (4). This paper describes a second case of Gorlin syndrome mosaicism with the same SMO L412F mutation observed in affected skin. A detailed molecular assessment of multiple BCNs and BCCs was performed to analyse the oncogenic steps of BCC formation in this patient. [ABSTRACT FROM AUTHOR]