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https://hdl.handle.net/2440/6918
Type: | Journal article |
Title: | Most germ-line mutations in the nevoid basal cell carcinoma syndrome lead to a premature termination of the PATCHED protein, and no genotype-phenotype correlations are evident |
Author: | Wicking, C. Shanley, S. Smyth, I. Gillies, S. Negus, K. Graham, S. Suthers, G. Haites, N. Edwards, M. Wainwright, B. Chenevix Trench, G. |
Citation: | American Journal of Human Genetics, 1997; 60(1):21-26 |
Issue Date: | 1997 |
ISSN: | 0002-9297 1537-6605 |
Abstract: | The human homologue of the Drosophila segment polarity gene patched is implicated in the development of nevoid basal cell carcinoma syndrome (NBCCS) and in the genesis of sporadic basal cell carcinomas. In order to examine the phenotypic variability in NBCCS and to highlight functionally important domains of the PTCH protein, we have now screened 71 unrelated NBCCS individuals for mutations in the PTCH exons. We identified 28 mutations that are distributed throughout the entire gene, and most (86%) cause protein truncation. As part of this analysis, we demonstrate that failure of one NBCCS family to show clear linkage to chromosome 9q22.3-31 is most likely due to germinal mosaicism. We have identified three families bearing identical mutations with variable phenotypes, suggesting phenotypic variability in NBCCS is a complex genetic event. No phenotype genotype correlation between the position of truncation mutations and major clinical features was evident. Two missense mutations have been identified, and their location within transmembrane domains supports the notion that PTCH may have a transport function. The preponderance of truncation mutants in the germ line of NBCCS patients suggests that the developmental defects associated with the disorder are most likely due to haploinsufficiency. |
Keywords: | Humans Basal Cell Nevus Syndrome Membrane Proteins Receptors, Cell Surface Pedigree Transcription, Genetic Genotype Phenotype Mosaicism Germ-Line Mutation Polymorphism, Single-Stranded Conformational Exons Molecular Sequence Data Female Male Patched Receptors Patched-1 Receptor |
Appears in Collections: | Aurora harvest 5 Paediatrics publications |
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