Please use this identifier to cite or link to this item:
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
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
Transcription, Genetic
Germ-Line Mutation
Polymorphism, Single-Stranded Conformational
Molecular Sequence Data
Patched Receptors
Patched-1 Receptor
Appears in Collections:Aurora harvest 5
Paediatrics publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.