OBJECTIVE: To identify the gene causing diffuse palmoplantar keratoderma in a Chinese pedigree. METHODS: Four normal individuals and 3 patients in a diffuse palmoplantar keratoderma family and 10 unrelated control samples were recruited. The hotspot of the mutations of keratin 9 gene was analyzed by polymerase chain reaction and direct sequencing. RESULTS: We found a G485A transition in ke ratin 9 gene, resulting in the substitution of glutamine for arginine at codon 162 in this diffuse palmoplantar keratoderma family. The mutation was not found in the 10 unrelated control samples and 4 normal individuals. CONCLUSION The mutation G485A found in keratin 9 gene is the disease-causing mutation in the diffuse palmoplantar keratoderma family.
Base Sequence ; DNA Mutational Analysis ; Female ; Heterozygote ; Humans ; Keratins ; genetics ; Keratoderma, Palmoplantar, Diffuse ; genetics ; Male ; Molecular Sequence Data ; Mutation ; Pedigree

In Drosophila, rhomboid proteases are active cardinal regulators of epidermal growth factor receptor (EGFR) signaling pathway. iRhom1 and iRhom2, which are inactive homologs of rhomboid intramembrane serine proteases, are lacking essential catalytic residues. These are necessary for maturation and trafficking of tumor necrosis factor-alpha (TNF-α) converting enzyme (TACE) from endoplasmic reticulum (ER) to plasma membrane through Golgi, and associated with the fates of various ligands for EGFR. Recent studies have clarified that the activation or downregulation of EGFR signaling pathways by alteration of iRhoms are connected to several human diseases including tylosis with esophageal cancer (TOC) which is the autosomal dominant syndrom, breast cancer, and Alzheimer's disease. Thus, this review focuses on our understanding of iRhoms and the involved mechanisms in the cellular processes.
Alzheimer Disease ; Breast Neoplasms ; Cell Membrane ; Down-Regulation ; Drosophila ; Endoplasmic Reticulum ; Esophageal Neoplasms ; Humans ; Keratoderma, Palmoplantar, Diffuse ; Ligands ; Peptide Hydrolases ; Receptor, Epidermal Growth Factor ; Serine Proteases ; Tumor Necrosis Factor-alpha

The hereditary epidermolytic palmoplantar keratoderma (Vorner"s kerato derma) is characterized by autosomal dominantly inherited, marked, symmetrical thickening of the palms and soles. The presence of epidermolytic hyperkeratosis in skin biopsy differentiates hereditary epidermolytic palmoplantar keratoderma from Unna-Thost keratoderma. We report a case of hereditary epidermolytic palmoplantar keratoderma with literature reviews focused on the differential points from other palmoplantar keratodermas.
Biopsy ; Hyperkeratosis, Epidermolytic ; Keratoderma, Palmoplantar ; Keratoderma, Palmoplantar, Epidermolytic* ; Skin

Palmoplantar keratodermas are divided into autosomal dominant and autosomal recessive groups by the mode of transmission. The autosomal dominantly transmitted group is further divided into epidermolytic and nonepidermolytic types according to the histological findings. Hereditary epidermolytic palmoplantar keratoderma manifests clinically as a localized thickening of the palms and soles. Herein we report a 29-year-old woman showing the typical clinical and histologic features of epidermolytic palmoplantar keratoderma without family history. This case could be spontaneous mutations that will later breed a true autosomal dominant trait.
Adult ; Female ; Humans ; Keratoderma, Palmoplantar ; Keratoderma, Palmoplantar, Epidermolytic*

We observed a family with 12 members in four consecutive generations affected by hereditary epidermolytic palmoplantar keratoderma(HEPPK). The affected family members demonstrated not only autosomal dominant inheritance, but also a high penetrance and constant expression. The lesion of all affected person had developed at birth or within the first few weeks of life. The lesions of three members(the proband, her sister and mother) were biopsed, and all of them showed the characteristic features of epidermolytic hyperkeratosis. Two of family members(the proband, her nephew-not affected by HEPPK) had vitiligo, but we concluded that this coexistance was accidental.
Family Characteristics* ; Humans ; Hyperkeratosis, Epidermolytic ; Keratoderma, Palmoplantar, Epidermolytic* ; Parturition ; Penetrance ; Siblings ; Vitiligo ; Wills

Epidermolytic keratosis palmaris is a rare disease which shows clinical findings of Unna Thost keratoderma and histopathologic of epidermolytic hyperkeratosis. We report herein a case of epidermolytic keratosis palmaris et plantaris in a 16-month-old female baby. Light microscopy shows marked hyperkeratosis, large irregular keratohyalin granules, and large clear spaces in the granular and upper spinous layers. Eletron microscopic findings shows that the clear spaces are areas of cytoplasm filled with a fibrillar material and cellular organelles. Abnormal clumping of tonofilament and keratohyalin is also present.
Cytoplasm ; Female ; Humans ; Hyperkeratosis, Epidermolytic ; Infant ; Intermediate Filaments ; Keratoderma, Palmoplantar* ; Keratosis* ; Microscopy ; Organelles ; Rare Diseases

In this article we reviewed the current researches on the molecular basis of epidermolytic palmoplantar keratoderma (EPPK) and the structure and function of the keratins with mutations that can cause inherited keratin disorders. Also summarized are seventeen mutations of keratin 9 in EPPK in different ethnic populations.
Humans ; Keratin-9 ; genetics ; physiology ; Keratoderma, Palmoplantar, Epidermolytic ; genetics ; pathology ; physiopathology ; Mutation

OBJECTIVETo map and identify the disease gene for the epidermolytic palmoplantar keratoderma (EPPK) in a Uighur family of China.

METHODSBlood samples were collected and genomic DNA was extracted from 48 members of the Xinjiang Uighur family. Six microsatellite repeat sequences on chromosome region 17q12-q21 and 12q13 were selected based on the two known candidate genes KRT9 and KRT1. Two-point linkage analysis and haplotype analysis were performed. Exons and their flanking intronic sequence of the KRT9 gene were amplified by polymerase chain reaction (PCR) and sequenced.

RESULTSData from the marker D17S1787 suggested linkage and yielded a Lod score of 8.65 at theta=0 by using MLINK software. Genotypes and haplotypes were acquired. The disease gene of the EPPK family is located between markers 17/TG/36620115 and D17S846. Chromosome 12q13 region was excluded with the negative Lod score obtained in marker D12S96 (Lod=-infinity at theta=0). No pathogenic mutation was detected in the KRT9 gene.

CONCLUSIONThe disease gene of the EPPK family is located on chromosome region 17q21.2. The keratin 9 gene might not be the disease gene.

China ; Chromosomes, Human, Pair 17 ; genetics ; Female ; Humans ; Keratin-1 ; genetics ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar, Epidermolytic ; ethnology ; genetics ; Male ; Microsatellite Repeats ; Mutation ; Pedigree

OBJECTIVETo analyze potential mutation of keration 9 gene (KRT9) in a Chinese family affected with epidermolytic palmoplantar keratoderma (EPPK) and to correlate genotype with the phenotype.

METHODSGenomic DNA was extracted from peripheral blood samples of 12 patients and 13 healthy individuals from the family and 100 unrelated individuals. Polymerase chain reaction (PCR) was used to amplify exons 1 and 6 of KRT9 gene. PCR products were sequenced bidirectionally in order to identify potential mutations.

RESULTSA heterozygous transversional mutation, 488G→A, was identified in exon 1 of KRT9 gene in all patients, which has resulted in substitution of a glutamine residue for arginine acid at position 163 (R163Q) of the KRT9 protein. The same mutation was not found in the 13 healthy members from the family and 100 unrelated individuals.

CONCLUSIONThe 488G→A mutation of KRT9 gene is probably the cause of EPPK in this Chinese family.

Adult ; Base Sequence ; DNA Mutational Analysis ; methods ; Female ; Humans ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar, Epidermolytic ; genetics ; Male ; Molecular Sequence Data ; Mutation

BACKGROUND: Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant disease of cornification which presents as severe thickening of the palms and soles with prominent epidermolytic hyperkeratosis pathologically. Recent studies have shown that EPPK is caused by mutations in the keratin 9 (K9) gene which is expressed essentially only in the palms and soles. Previously, We have reported that patients in one large pedigree of EPPK have an R162W substitution in the K9 protein. In this pedigree, two women whose husbands are both EPPK patients had become pregnant. OBJECTIVE: Since both women were concerned about this genetic disorder, we have performed prenatal diagnosis by biopsy analysis of chorionic villi tissue. METHODS: Chorionic villi biopsies were performed at 12 weeks gestation. Since the skin lesions are strictly confined to the palms and soles of the babies, the prenatal diagnosis of EPPK by ultrastructural analysis of fetal skin biopsy or amniotic fluid cells is highly problematic. Polymerase chain reaction amplification of specific allele (PASA) assay and direct DNA sequencing analyses were performed whether the fetuses carried mutant allele of K9 gene. RESULTS: PASA assay and direct DNA sequencing analyses showed that one fetus was normal, but the other fetus carried the abnormal allele. Subsequently, the mother of the unaffected fetus delivered a normal child, but the mother of the affected fetus terminated the pregnancy. CONCLUSION: We describe the analysis of the K9 mutation in the two fetuses at risk for EPPK. We believe that this is the first report of prenatal diagnosis for EPPK. But, we have to think about the ethical problems before we decide to perform the prenatal diagnosis of any kind of skin diseases.
Alleles ; Amniotic Fluid ; Biopsy ; Child ; Chorionic Villi ; Chorionic Villi Sampling ; Female ; Fetus ; Humans ; Hyperkeratosis, Epidermolytic ; Keratin-9 ; Keratoderma, Palmoplantar, Epidermolytic* ; Mothers ; Pedigree* ; Polymerase Chain Reaction ; Pregnancy* ; Prenatal Diagnosis* ; Sequence Analysis, DNA ; Skin ; Skin Diseases ; Spouses