title: A novel KRT86 mutation in a Turkish family with monilethrix, and identification of maternal mosaicism.
abstract: BACKGROUND
  Monilethrix is a rare monogenic dystrophic hair loss disorder with high levels of intrafamilial and interfamilial variability. It is characterized by diffuse occipital or temporal alopecia, hair fragility and follicular hyperkeratosis of the occipital region. Mutations in the keratin genes KRT81, KRT83 and KRT86 lead to autosomal dominant monilethrix, whereas mutations in the desmoglein 4 gene (DSG4) cause an autosomal recessive form.
  
  
  OBJECTIVE
  To identify the mutation in a consanguineous Turkish family with three affected children and apparently unaffected parents.
  
  
  METHODS
  Sequencing analysis of the genes DSG4 and KRT86 was performed. SNaPshot analysis was conducted to quantify the proportion of cells carrying the KRT86 mutation and to confirm maternal mosaicism of KRT86.
  
  
  RESULTS
  No pathogenic mutation was found by sequencing analysis of DSG4; however, analysis of KRT86 revealed a novel mutation, c.1231G>T;p.Glu411*, in exon 7 in the three affected children and their mother. The mutation signal was weaker in the mother than in the three siblings, and SNaPshot analysis revealed substantial mutation-level variation between the children and their mother.
  
  
  CONCLUSIONS
  Our results extend the spectrum of KRT86 mutations and indicate KRT86 mosaicism in the family examined. This study is the first, to our knowledge, to describe mosaicism for a monogenic hair loss disorder, and suggests that mosaicism leads to a mild manifestation of monilethrix.
authors: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors: S
authors: S
authors: Redler
authors: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors: S M
authors: SM
authors: Pasternack
authors: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
authors: S
authors: S
authors: Wolf
authors: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors: D
authors: D
authors: Stienen
authors: Department of Dermatology, University of Bonn, Bonn, Germany.
authors: J
authors: J
authors: Wenzel
authors: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
authors: M M
authors: MM
authors: Nöthen
authors: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors: R C
authors: RC
authors: Betz
mesh_terms: D000293:Adolescent; D044466:Asian People; D002648:Child; D051182:Desmogleins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D053564:Keratins, Hair-Specific / Q000235:genetics*; D053531:Keratins, Type II / Q000235:genetics*; D008297:Male; D056734:Monilethrix / Q000235:genetics*; D009030:Mosaicism; D009154:Mutation; D010375:Pedigree; D014421:Turkey
chemical_list: C473409:DSG4 protein, human; D051182:Desmogleins; C507605:KRT86 protein, human; D053564:Keratins, Hair-Specific; D053531:Keratins, Type II