Further Expanding the Mutational Spectrum of Gorlin Syndrome in Three Unrelated Families

Abstract

<b><i>Introduction:</i></b> Gorlin syndrome is a rare, autosomal dominant multi-systemic disorder with a predisposition to the development of cancers such as medulloblastoma and nevoid basal cell carcinoma. Heterozygous pathogenic variants in <i>PTCH1</i> are responsible for 90% of Gorlin syndrome cases. Pathogenic variants in <i>PTCH1</i> cause overstimulation of the sonic hedgehog signaling pathway, which plays a role in the development of embryonic structures and tumorigenesis. Clinical major and minor diagnostic criteria for Gorlin syndrome have been determined. Odontogenic keratocyst (OKC) is the most common reason for medical admission in Gorlin syndrome. In this article, it is aimed to draw attention to the fact that patients with Gorlin syndrome are not very rare in our country and the variability in phenotypic and dysmorphic findings may be a clue for the diagnosis. <b><i>Methods:</i></b> Exome sequencing was performed on the Illumina NextSeq550 System platform by using the Ion Ampliseq exome RDY kit for Illumina. Sanger sequencing was performed accordingly for the other affected individuals in both families. <b><i>Results:</i></b> In this study, the clinical and molecular findings of 9 Gorlin syndrome patients from three unrelated families are presented. Macrocephaly, calcification of falx cerebri, palmar-plantar pits, rib anomalies, and OKC were detected in decreasing order in more than half of the patients. A novel heterozygous frameshift <i>PTCH1</i> variant in family 1, a nonsense previously reported <i>PTCH1</i> variant in family 2, and a novel heterozygous splice-site <i>PTCH1</i> variant in family 3 were detected. <b><i>Conclusion:</i></b> Gorlin syndrome should be kept in mind in patients presenting with macrocephaly, palmoplantar pits, and OKC history. Careful examination of all family members is essential in the timely diagnosis of other affected individuals with minor phenotypic findings.