Selective haploinsufficiency of longer isoforms of PTCH1 protein can cause nevoid basal cell carcinoma syndrome

Journal of Human Genetics
Maiko SuzukiT Miyashita

Abstract

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.

References

Mar 1, 1987·Medicine·R J Gorlin
Mar 31, 1997·American Journal of Medical Genetics·V E KimonisS J Bale
Dec 4, 2001·Genes & Development·P W Ingham, A P McMahon
Aug 31, 2002·Science·David M BermanPhilip A Beachy
May 5, 1960·The New England Journal of Medicine·R J GORLIN, R W GOLTZ
Jul 31, 2004·Nature Genetics·Jill A HolbrookAndreas E Kulozik
Aug 29, 2006·Biochemical and Biophysical Research Communications·Hideki UchikawaToshiyuki Miyashita

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Citations

Sep 25, 2014·American Journal of Hematology·Juan M Alonso-DominguezGareth Gerrard
Aug 19, 2014·Pediatrics International : Official Journal of the Japan Pediatric Society·Katsunori Fujii, Toshiyuki Miyashita
Jun 23, 2018·Journal of Human Genetics·Robbert-Jan C A M GielenMichel van Geel
Apr 19, 2019·Medical Molecular Morphology·Junfeng ZhouXiaoliu Shi

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