title: Somatic mosaicism containing double mutations inPTCH1revealed by generation of induced pluripotent stem cells from nevoid basal cell carcinoma syndrome.
abstract: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterised by developmental defects and tumorigenesis, such as medulloblastomas and basal cell carcinomas, caused by mutations of thepatched-1(PTCH1) gene. In this article, we seek to demonstrate a mosaicism containing double mutations inPTCH1in an individual with NBCCS.
  
  
  
  A de novo germline mutation ofPTCH1(c.272delG) was detected in a 31-year-old woman with NBCCS. Gene analysis of two out of four induced pluripotent stem cell (iPSC) clones established from the patient unexpectedly revealed an additional mutation, c.274delT. Deep sequencing confirmed a low-prevalence somatic mutation (5.5%-15.6% depending on the tissue) identical to the one found in iPSC clones.
  
  
  
  This is the first case of mosaicism unequivocally demonstrated in NBCCS. Furthermore, the mosaicism is unique in that the patient carries one normal and two mutant alleles. Because these mutations are located in close proximity, reversion error is likely to be involved in this event rather than a spontaneous mutation. In addition, this study indicates that gene analysis of iPSC clones can contribute to the detection of mosaicism containing a minor population carrying a second mutation.
authors.affiliation: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.|Center for Regenerative Medicine, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ikemoto
authors.affiliation: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.|Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Takayama
authors.affiliation: Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Fujii
authors.affiliation: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.
authors.forename: Mokuri
authors.initials: M
authors.lastname: Masuda
authors.affiliation: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.
authors.forename: Chise
authors.initials: C
authors.lastname: Kato
authors.affiliation: Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hatsuse
authors.affiliation: Gene Analysis Center, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Fujitani
authors.affiliation: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.|Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nagao
authors.affiliation: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.|Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Kameyama
authors.affiliation: Center for Regenerative Medicine, National Research Institute for Child Health and Development, Tokyo, Japan.|Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Ikehara
authors.affiliation: Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Toyoda
authors.affiliation: Center for Regenerative Medicine, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.affiliation: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.|Department of Molecular Genetics, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyashita
mesh_terms: D000328:Adult; D000483:Alleles; D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D009030:Mosaicism; D000072081:Patched-1 Receptor / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: C000606236:PTCH1 protein, human; D000072081:Patched-1 Receptor
keywords: Mosaicism AND two mutations; PTCH1; deep sequencing; nevoid basal cell carcinoma syndrome