期刊
JOURNAL OF HUMAN GENETICS
卷 57, 期 7, 页码 422-426出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/jhg.2012.45
关键词
alternative splicing; nevoid basal cell carcinoma syndrome; PTCH1
资金
- Ministry of Education, Culture, Sports, Science and Technology [20591261]
- Ministry of Health, Labour
- Grants-in-Aid for Scientific Research [23501269, 20591261] Funding Source: KAKEN
Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis. The gene responsible for NBCCS is PTCH1. The PTCH1 gene has five alternatively used first exons resulting in the translation of three isoforms of the PTCH1 protein; that is, PTCHL, PTCHM and PTCHS. However, the biological significance of each isoform is unclear. Here we show an individual with NBCCS carrying a nonsense mutation in PTCH1 exon2, c. 387G > A (p.W129X). As the mutation lay upstream of the ATG codon used for PTCHS translation, the mutant allele still expressed RNA isoforms that encode PTCHS. These results clearly demonstrate that a selective haploinsufficiency of longer isoforms of the PTCH1 protein, PTCHL and PTCHM, but not PTCHS is sufficient to cause NBCCS. Although mice selectively deficient in PTCHS isoforms are currently unavailable, this study sheds light on the complex in vivo roles of PTCH1 isoforms. Journal of Human Genetics (2012) 57, 422-426; doi:10.1038/jhg.2012.45; published online 10 May 2012
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