title: Identification of factors contributing to phenotypic divergence via quantitative image analyses of autosomal recessive woolly hair/hypotrichosis with homozygous c.736T>A LIPH mutation.
abstract: BACKGROUND
  Autosomal recessive woolly hair/hypotrichosis (ARWH/H) is caused by mutations in LIPH. Homozygotes for the LIPH c.736T>A (p.C246S) mutation, the most prevalent genotype in Japanese patients, present varying degrees of hair loss; however, determinants of this phenotypic diversity remain elusive.
  
  
  OBJECTIVE
  To establish methodologies for quantitative assessment of clinical severity and provide a detailed characterization to elucidate the factors contributing to phenotypic divergence.
  
  
  METHODS
  Digital image analyses were conducted to convert clinical severities into numerical values. Eight patients with ARWH/H were classified into three groups (mild, severe, very severe), based on severity scores. Dermoscopic images were collected and assessed for total hair numbers and hair thickness for intergroup comparisons.
  
  
  RESULTS
  The image analysis detected a difference in hair thickness but not in total hair numbers, between mild and severe cases. A marked decrease in total hair number was noted in an atypical very severe case. Histopathologically, a patient with a mild case demonstrated hair miniaturization and a high telogen/anagen ratio without a decrease in total hair count, endorsing dermoscopic observations. Two children demonstrated spontaneous improvement without an increase in total hair numbers, and two adults responded well to topical minoxidil with increased total hair numbers and hair thickness.
  
  
  CONCLUSIONS
  The difference in the frequency of underdeveloped hairs may be a major factor contributing to the clinical diversity of hair sparseness in LIPH c.736T>A homozygotes with ARWH/H. Hence, pharmacological modification to thicken existing fine hairs may provide a therapeutic strategy.
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.|Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kinoshita-Ise
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kubo
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.|KOSÉ Endowed Program for Skin Care and Allergy Prevention, Keio University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Umegaki-Arao
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Amagai
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.|Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohyama
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D046169:Dermoscopy / Q000379:methods; D005260:Female; D006197:Hair / Q000002:abnormalities* / Q000473:pathology*; D006201:Hair Diseases / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006203:Hair Preparations / Q000627:therapeutic use; D006720:Homozygote; D006801:Humans; D007039:Hypotrichosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008049:Lipase / Q000235:genetics*; D008297:Male; D008914:Minoxidil / Q000627:therapeutic use; D009154:Mutation / Q000235:genetics; D010641:Phenotype
chemical_list: D006203:Hair Preparations; C504173:LIPC protein, human; D008914:Minoxidil; D008049:Lipase