title: Familial progressive hyper- and hypopigmentation and malignancy in two families with new mutations in KITLG.
abstract: BACKGROUND
  Familial progressive hyper- and hypopigmentation (FPHH) is an autosomal dominant skin condition presenting in childhood with generalized macular dyspigmentation, usually reported in patients of East Asian origin. It overlaps phenotypically with other dyschromatoses, but can now be distinguished by mutations in the KIT ligand gene (KITLG).
  
  
  OBJECTIVE
  We report two unrelated white families with similar phenotypic presentations of FPHH developing in early childhood in several generations.
  
  
  METHODS
  Sanger sequencing of the exons and flanking introns of KITLG was performed.
  
  
  RESULTS
  This identified a new heterozygous missense mutation in each family (p.Thr34Asn and p.Val37Gly, respectively). Of the six affected individuals examined by us, two had cancer: a 62-year-old man in family 1 had developed two primary melanomas and a pharyngeal carcinoma, and a 42-year-old woman in family 2 had developed thyroid carcinoma. All had unusually sparse lateral eyebrows, a finding not previously reported in this condition.
  
  
  CONCLUSIONS
  We summarize the genetic spectrum of the dyschromatoses and discuss a possible increased risk of malignancy in FPHH.
authors.affiliation: Department of Dermatology, Birmingham Children's Hospital, NHS Foundation Trust, Birmingham, UK.
authors.forename: A
authors.initials: A
authors.lastname: Cuell
authors.affiliation: Department of Dermatology, Solihull Hospital, Heart of England NHS Foundation Trust, Solihull, UK.
authors.forename: N
authors.initials: N
authors.lastname: Bansal
authors.affiliation: Department of Clinical Genetics, Birmingham Women's Hospital, NHS Foundation Trust, Birmingham, UK.
authors.forename: T
authors.initials: T
authors.lastname: Cole
authors.affiliation: Department of Dermatology, Solihull Hospital, Heart of England NHS Foundation Trust, Solihull, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Kaur
authors.affiliation: Genetic Skin Disease Group, St John's Institute of Dermatology, King's College London, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Solihull Hospital, Heart of England NHS Foundation Trust, Solihull, UK.
authors.forename: A
authors.initials: A
authors.lastname: Loffeld
authors.affiliation: Department of Dermatology, Birmingham Children's Hospital, NHS Foundation Trust, Birmingham, UK.
authors.forename: C
authors.initials: C
authors.lastname: Moss
authors.affiliation: Department of Clinical Genetics, Birmingham Women's Hospital, NHS Foundation Trust, Birmingham, UK.
authors.forename: M
authors.initials: M
authors.lastname: O'Donnell
authors.affiliation: Genetic Skin Disease Group, St John's Institute of Dermatology, King's College London, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Takeichi
authors.affiliation: Department of Dermatology, Birmingham Children's Hospital, NHS Foundation Trust, Birmingham, UK.
authors.forename: C K
authors.initials: CK
authors.lastname: Thind
authors.affiliation: Genetic Skin Disease Group, St John's Institute of Dermatology, King's College London, London, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D006801:Humans; D017495:Hyperpigmentation / Q000235:genetics*; D017496:Hypopigmentation / Q000235:genetics*; D007438:Introns; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009369:Neoplasms / Q000150:complications; D010375:Pedigree; D019089:Stem Cell Factor / Q000235:genetics*
chemical_list: D019089:Stem Cell Factor