title: Hereditary leukonychia, or porcelain nails, resulting from mutations in PLCD1.
abstract: Hereditary leukonychia (porcelain nails or white nails) is a rare nail disorder with an unknown genetic basis. To identify variants in a gene underlying this phenotype, we identified four families of Pakistani origin showing features of hereditary leukonychia. All 20 nails of each affected individual were chalky and white in appearance, consistent with total leukonychia, with no other cutaneous, appendageal, or systemic findings. By using Affymetrix 10K chip, we established linkage to chromosome 3p21.3-p22 with a LOD score (Z) of 5.1. We identified pathogenic mutations in PLCD1 in all four families, which encodes phosphoinositide-specific phospholipase C delta 1 subunit, a key enzyme in phosphoinositide metabolism. We then identified localization of PLCD1 in the nail matrix. It was recently shown that PLCD1 is a component of the human nail plate by proteomic analysis and is localized in the matrix of human nails. Furthermore, mutations detected in PLCD1 resulted in reduced enzymatic activity in vitro. Our data show that mutations in PLCD1 underlie hereditary leukonychia, revealing a gene involved in molecular control of nail growth.
authors.affiliation: Department of Dermatology, Columbia University, New York, NY 10032, USA.
authors.forename: Maija
authors.initials: M
authors.lastname: Kiuru
authors.affiliation: Department of Dermatology, Columbia University, New York, NY 10032, USA.
authors.forename: Mazen
authors.initials: M
authors.lastname: Kurban
authors.affiliation: Department of Dermatology, Columbia University, New York, NY 10032, USA.
authors.forename: Munenari
authors.initials: M
authors.lastname: Itoh
authors.affiliation: Department of Dermatology, Columbia University, New York, NY 10032, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Petukhova
authors.affiliation: Department of Dermatology, Columbia University, New York, NY 10032, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimomura
authors.affiliation: Department of Dermatology, Columbia University, New York, NY 10032, USA.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wajid
authors.affiliation: Department of Dermatology, Columbia University, New York, NY 10032, USA; Department of Genetics and Development, Columbia University, New York, NY 10032, USA. Electronic address: amc65@columbia.edu.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D006801:Humans; D017496:Hypopigmentation / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009260:Nail Diseases / Q000151:congenital / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009262:Nails / Q000196:embryology / Q000201:enzymology / Q000473:pathology*; D010375:Pedigree; D054803:Phospholipase C delta / Q000235:genetics* / Q000378:metabolism
chemical_list: C518024:PLCD1 protein, human; D054803:Phospholipase C delta