The Hedgehog signalling pathway is involved in regulation of differentiation of embryonic cells, in body patterning, in development of brain, bone, muscle, gastrointestinal tract, lungs, and in maintenance and regeneration of adult tissues. The pathway includes more than 10 proteins: receptors, coreceptors, ligands, transcription effectors and repressors, linked in complex functional interactions. Disruption of the hedgehog signalling during embryogenesis can lead to a serious developmental disorder - to holoprosencephaly. Loss-of- function mutations of PTCH1 lead to Gorlin syndrome - a hereditary predisposition to basal cell carcinoma associated with anomalies of brain, scull, vertebrae, and ribs. Both holoprosencephaly and Gorlin syndrome have been shown to be genetically heterogeneous, both can be caused by germline mutations of several genes of the Hedgehog signalling pathway. From 2006 to 2016, the PTCH1 gene was analysed for diagnostic purposes in 70 unrelated patients with suspicion of Gorlin syndrome (MIM 109400) referred to the Department of Biology and Medical Genetics, 2nd Medical School and University Hospital Motol, Prague. A pathogenic variant of the PTCH1 gene was detected in 35 (50%) of patients. No mutation was found in 35 patients, 10 of them fulfilled, and 25 of them did not...