title: A Frameshift Mutation in PEN-2 Causes Familial Comedones Syndrome.
abstract: BACKGROUND
  Familial comedones without dyskeratosis are a rare autosomal dominant skin disorder, characterized by the occurrence of comedones that are distributed all over the body with specific features. We have previously reported two Thai families with familial comedones with expanded phenotypic spectrum. However, its genetic defect and pathogenesis remain unknown.
  
  
  OBJECTIVE
  To explore the molecular defect causing familial comedones.
  
  
  METHODS
  Whole-genome linkage analysis and whole-exome sequencing in family I were performed.
  
  
  RESULTS
  We identified a heterozygous one-base pair insertion, c.84_85insT (p. L28FfsX93) in PEN-2, located within the linked region on chromosome 19. PCR-Sanger sequencing confirmed the identified mutation. The mutation segregated with the disease phenotype in family I and was fully penetrant. This similar mutation was also present in the unrelated affected individual from family II. Quantitative PCR revealed increased mRNA expression of PEN-2 in leukocytes of affected individuals.
  
  
  CONCLUSIONS
  We for the first time identify PEN-2 as the causative gene of familial comedones.
authors.affiliation: Center of Excellence for Medical Genetics, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Wipa
authors.initials: W
authors.lastname: Panmontha
authors.forename: Pawinee
authors.initials: P
authors.lastname: Rerknimitr
authors.forename: Patra
authors.initials: P
authors.lastname: Yeetong
authors.forename: Chalurmpon
authors.initials: C
authors.lastname: Srichomthong
authors.forename: Kanya
authors.initials: K
authors.lastname: Suphapeetiporn
authors.forename: Vorasuk
authors.initials: V
authors.lastname: Shotelersuk
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012868:Skin Abnormalities / Q000235:genetics*; D017444:Skin Diseases, Papulosquamous / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C469349:PSENEN protein, human; D053829:Amyloid Precursor Protein Secretases