title: Analysis of mutation in exon 17 of PTCH in patients with nevoid basal cell carcinoma syndrome.
abstract: Abnormalities in sonic hedgehog (SHH) signaling pathway components are major contributing factors in the development of nevoid basal cell carcinoma syndromes (NBCCS) that include SHH, PTCH, SMO and GLI. The novel patched homologue (PTCH) mutation and clinical manifestations with NBCCS links PTCH haplosufficiency and aberrant activation of the sonic hedgehog/Patched/smoothened pathway. To investigate further the molecular genetics of NBCCS, we performed mutation analysis of PTCH gene in a family case with five affected members. These clinical manifestations might be associated with a novel constitutional mutation of the PTCH gene, 3146A-->T (1049N-->I), in exon 17. The analyzed results of tumor tissue show a high expression of GLI. Our findings suggested that the mutation of 3146A-->T may be the cause of high expression of GLI and permit SMO to transmit signal to the nucleus through SHH/PTCH/SMO pathway.
authors.affiliation: Department of Oral Maxillofacial Surgery, School of Stomatology, Harbin Medical University, Harbin, China.
authors.forename: Jichen
authors.initials: J
authors.lastname: Li
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wang
authors.forename: Yingqun
authors.initials: Y
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D001478:Basal Cell Nevus Syndrome / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1