title: Homozygous deletion of six genes including corneodesmosin on chromosome 6p21.3 is associated with generalized peeling skin disease.
abstract: BACKGROUND
  Peeling skin syndrome (PSS) is a rare autosomal recessive form of ichthyosis showing skin exfoliation. PSS is divided into acral and generalized PSS, and the latter is further classified into non-inflammatory type (PSS type A) and inflammatory type (PSS type B). PSS type B is now called peeling skin disease (PSD). Different loss-of-function mutations in the corneodesmosin (CDSN) gene have been reported to cause PSD.
  
  
  OBJECTIVE
  The aim of this study was to determine genetic basis of disease in a 14-year-old Japanese patient with PSD.
  
  
  RESULTS
  Immunohistochemical study showed lack of corneodesmosin (CDSN) in the skin, and standard PCR for genomic DNA failed to amplify CDSN product, suggesting CDSN defect. Multiplex ligation-dependent probe amplification and genomic quantitative real-time PCR analyses detected large homozygous deletion of 59,184bp extending from 40.6kb upstream to 13.2kb downstream of CDSN, which included 6 genes (TCF19, CCHCR1, PSORS1C2, PSORS1C1, CDSN and C6orf15). The continuous gene lost did not result in additional clinical features. Inverted repeats with 85% similarity flanking the deletion breakpoint were considered to mediate the deletion by non-homologous end joining or fork stalling and template switching/microhomology-mediated break-induced replication. Parents were clinically unaffected and were heterozygote carriers of the same deletion, which was absent in 284 ethnically matched control alleles. We also developed simple PCR method, which is useful for detection of this deletion.
  
  
  CONCLUSIONS
  Although 5 other genes were also deleted, homozygous deletion of CDSN was considered to be responsible for this PSD.
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Kwesi
authors.initials: K
authors.lastname: Teye
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hamada
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Rafal P
authors.initials: RP
authors.lastname: Krol
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Numata
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Norito
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Matsuda
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Ohata
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Minao
authors.initials: M
authors.lastname: Furumura
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Fukuoka 830-0011, Japan. Electronic address: hashimot@med.kurume-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002896:Chromosomes, Human, Pair 6; D003873:Dermatitis, Exfoliative / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012867:Skin / Q000737:chemistry / Q000473:pathology; D012873:Skin Diseases, Genetic / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
chemical_list: C109656:CDSN protein, human; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins
keywords: CDSN; Gene deletion; MLPA; Peeling skin syndrome; qPCR