How to Cite this Article: Kosaki R, Nagao K, Kameyama K, Suzuki M, Fujii K, Miyashita T. 2012. Heterozygous tandem duplication within the PTCH1 gene results in nevoid basal cell carcinoma syndrome. Am J Med Genet Part A. 158A:1724–1728.
Heterozygous tandem duplication within the PTCH1 gene results in nevoid basal cell carcinoma syndrome†
Version of Record online: 7 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 7, pages 1724–1728, July 2012
How to Cite
Kosaki, R., Nagao, K., Kameyama, K., Suzuki, M., Fujii, K. and Miyashita, T. (2012), Heterozygous tandem duplication within the PTCH1 gene results in nevoid basal cell carcinoma syndrome. Am. J. Med. Genet., 158A: 1724–1728. doi: 10.1002/ajmg.a.35412
- Issue online: 18 JUN 2012
- Version of Record online: 7 JUN 2012
- Manuscript Accepted: 18 MAR 2012
- Manuscript Received: 10 NOV 2011
- Ministry of Health, Labour and Welfare
- Ministry of Education, Culture, Sports, Science and Technology 20591261
- nevoid basal cell carcinoma syndrome;
- tandem duplication
Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis. The gene responsible for NBCCS is PTCH1. Using multiplex ligation-dependent probe amplification, we identified a heterozygous tandem duplication within the PTCH1 gene in a 14-year-old girl with typical NBCCS. We have sequenced the chromosomal breakpoint and determined the duplication as tandem in orientation and 18,814 bp in size. The fusion occurred between non-repetitive elements with an overlap of three nucleotides. The duplicated segment began at exon 10 and ended at intron 17. Subsequent analysis of cDNA from the patient showed the expression of mutant mRNA species containing a duplicated segment spanning exons 11–17, resulting in a frameshift and premature stop codon. This is the first reported case of NBCCS due to a tandem multiexon duplication of PTCH1 representing a novel mechanism leading to the NBCCS phenotype, and highlights the importance of copy number analysis as an adjunct to exon sequencing in identifying infrequent mutational events in PTCH1. © 2012 Wiley Periodicals, Inc.