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.
Subject(s)
Chromosomes, Human, Pair 3/genetics , Nails/pathology , Phospholipase C delta/genetics , Humans , Hypopigmentation/enzymology , Hypopigmentation/genetics , Hypopigmentation/pathology , Mutation , Nail Diseases/congenital , Nail Diseases/enzymology , Nail Diseases/genetics , Nail Diseases/pathology , Nails/embryology , Nails/enzymology , Pedigree , Phospholipase C delta/metabolismABSTRACT
Genotyping of polymorphic drug metabolizing enzymes may be useful to estimate the blood concentration, efficacy, and toxicity of drugs before administration. Blood samples are most generally used for genotyping; however, sampling is invasive and complicated by handling and transport. Therefore, the authors developed genotyping methods using nonblood specimens, and then each genotype was compared with that from blood. Healthy Japanese volunteers provided hairs (n = 50), buccal cell swabs (n = 50), and fingernails (n = 30) for N-acetyltransferase 2 and CYP2C19 genotyping. Recovery of genomic DNA from each nonblood specimen was lower than that from 0.5 mL blood. Using a modification of the DNA extraction and polymerase chain reaction amplification method, genotypes were diagnosed without failure, even for those with very low levels of DNA. Both genotypes from these specimens completely matched the genotypes from the blood of the same subject. These nonblood specimens can be convenient, accessible, and economical alternatives to blood as a source of DNA for genotyping.
Subject(s)
Aryl Hydrocarbon Hydroxylases , Arylamine N-Acetyltransferase/genetics , Cytochrome P-450 Enzyme System/genetics , Hair/enzymology , Mixed Function Oxygenases/genetics , Mouth Mucosa/enzymology , Nails/enzymology , Arylamine N-Acetyltransferase/metabolism , Blood , Cytochrome P-450 CYP2C19 , Cytochrome P-450 Enzyme System/metabolism , DNA/analysis , DNA Primers/chemistry , Fingers/physiology , Genotype , Humans , Mixed Function Oxygenases/metabolism , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthSubject(s)
Amino Acid Metabolism, Inborn Errors/enzymology , Chromatography, High Pressure Liquid , Histidine Ammonia-Lyase/analysis , Histidine/blood , Nails/enzymology , Histidine Ammonia-Lyase/deficiency , Histidine Ammonia-Lyase/metabolism , Humans , Nails/chemistry , Urocanic Acid/analysis , Urocanic Acid/metabolismABSTRACT
X-linked ichthyosis is generally diagnosed by a deficiency of steroid sulfatase activity in fibroblasts or leukocytes. We established a method of assaying nail steroid sulfatase activity for diagnostic use. Nail samples were easy to collect and handle, and satisfied the screening criteria of accuracy, sensitivity, and stability. The detergents Tween 20 and Triton-X 100, which enhance nail STS activity, enabled us to assay the activity with small amounts of nails. The detergent-facilitated assay was also suitable for use with pediatric patients, from whom small amounts of nails were collected.
Subject(s)
Arylsulfatases/metabolism , Ichthyosis, X-Linked/diagnosis , Nails/enzymology , Adult , Arylsulfatases/deficiency , Child , Child, Preschool , Female , Fingers , Humans , Ichthyosis, X-Linked/epidemiology , Ichthyosis, X-Linked/genetics , Infant , Male , Middle Aged , Steryl-SulfataseABSTRACT
Arylsulfatases A and B were measured in the stratum corneum of four normal controls and two individuals with sex-linked ichthyosis. For arylsulfatase A, the mean delta optical density/hr/mg protein value was 1.6 for controls and 2.0 for patients, whereas for arylsulfatase B values of 1.5 for controls and 1.4 for patients were observed. Assay of arylsulfatase C in the callus of four normal controls showed a mean delta optical density/hr/100 mg callus of 0.63, whereas no or trace activity was detected in callus from four patients with x-linked ichthyosis. The assay of steroid sulfatase is best for studying microsomal sulfatase activity. Table 1 shows the activity of this enzyme in nails, callus, and hair bulbs from controls and patients with x-linked ichthyosis. No steroid sulfatase could be demonstrated in patients with x-linked ichthyosis. The values in normal controls and obligate heterozygotes are compared in Table 2. The mean value of the two groups is statistically different with P less than or equal to 0.05 using the Student t test.
