Whole-Exome Sequencing Identified Two Novel Pathogenic Mutations in the PTCH1 Gene in BCNS

Basal cell nevus syndrome (BCNS, OMIM 109400) is a familial cancer characterized by the development of numerous basal cancers and various other developmental abnormalities, including epidermal cysts skin, calcified dural folds, keratocysts jaw, palmar plantar pits, ovarian fibromas, medulloblastomas, lymphomesenteric cysts, fetal rhabdomyomas. BCNS shows autosomal dominant inheritance caused mutations in patched 1 (PTCH1) gene suppressor fused homolog (SUFU) gene. In few cases, variants 2 (PTCH2) have been found patients who met criteria for BCNS. an investigation 11 Hungarian families fulfilled diagnostic BCNS, whole-exome sequencing (WES) multiplex ligation-dependent probe amplification (MLPA) identified two novel pathogenic (c.2994C>A; p.Cys998Ter c.814_818del; p.Asn272SerfsTer11), one recently variant (c.1737_1745del p.Val580_Val582del), three recurrent disease-causing PTCH1 with diagnosis rate 63.6%. Disease-causing were not SUFU PTCH2 genes. These applied methods could fully elucidate genetic background all cases that we investigated. To uncover missing heritability whole-genome or epigenetic approach might be considered future.