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Results for “Keratoderma, Palmoplantar”

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At least 19 recordsLinked to original sources
PubMed1995

Ultrastructural changes resulting from keratin-9 gene mutations in two families with epidermolytic palmoplantar keratoderma.

Palmoplantar keratoderma of Voerner type (or epidermolytic palmoplantar keratoderma) is an autosomal dominant inherited disorder of keratinization with histologic features of epidermolytic hyperkeratosis. We studied members of two large unrelated kindreds with epidermolytic palmoplantar keratoderma, and biopsy specimens of lesional palmar skin from both families confirmed the histologic changes of epidermolytic hyperkeratosis. Whorls of abnormally aggregated keratin filaments were seen ultrastructurally to be associated with signs of cellular disintegration in spinous and granular cells. Direct sequencing of genomic DNA samples obtained from several members of each family established the substitution of a highly conserved arginine by tryptophan (R162W) in the 1A region of the alpha-helical rod domain of keratin 9. This arginine residue in a highly conserved region of keratins 1 and 10 is affected by disruptive missense point mutations in many patients with bullous ichthyosiform erythroderma. An equivalent position in the sole and palm restricted keratin 9 appears to be the mutation hot spot in epidermolytic palmoplantar keratoderma. To date, R162W is the most prevalent genetic defect reported in this genodermatosis.

Base Composition↗
PubMed1998

Mutations in the 1A rod domain segment of the keratin 9 gene in epidermolytic palmoplantar keratoderma.

Palmoplantar keratodermas (PPK) constitute a heterogeneous group of diseases marked by the thickening of palms and soles of affected individuals. They are divided into autosomal dominant and autosomal recessive groups by the mode of transmission. The autosomal dominantly transmitted group is further divided into epidermolytic (EPPK, Voerner) and non-epidermolytic (NEPPK, Unna-Thost) types according to the histopathologic findings. Recent development of molecular approaches has confirmed that EPPK and NEPPK are caused by the mutations in keratin 9 and 1 genes, respectively. We have studied three families of EPPK to find the mutation in the keratin 9 gene. DNA sequence analyses revealed single base changes in sequences encoding the highly conserved 1A rod domain segment of the keratin 9 gene in two of the three families. These mutations caused Arg (CGG) to Glu (CAG; R162Q) and Arg (CGG) to Try (TGG; R162W) substitutions. The same arginine position has been mutated in the keratin 10 gene in epidermolytic hyperkeratosis, the keratin 14 gene in epidermolysis bullosa simplex, and the keratin 9 gene in hereditary EPPK in Western patients. In this study we show that unrelated Korean patients have similar mutations.

Arginine↗
PubMed1990

Autosomal recessive epidermolytic palmoplantar keratoderma.

Palmoplantar keratoderma (PPK) is a heterogeneous group of disorders. Epidermolytic PPK is a well delineated autosomal dominant entity, but no recessive form is known. Here we report two sons of phenotypically normal, consanguineous, Arab parents with features suggestive of PPK. They presented with patchy eczematous skin lesions followed by PPK and raised serum levels of IgE. Skin biopsy from the keratotic lesions showed the features of epidermolytic hyperkeratosis. Autosomal recessive inheritance is suggested and the differential diagnosis is discussed.

Child, Preschool↗
PubMed2002

Non-small-cell lung cancer with nonfamilial diffuse palmoplantar keratoderma.

Palmoplantar keratoderma (PPK) is a congenital or acquired disorder characterized by the abnormal thickening of the skin of the palms and soles. The thickening can present as a diffuse, focal or punctate pattern. It has been reported to be associated with internal malignancies such as lung and esophageal carcinomas. When PPK is associated with malignancy the prognosis is poor. Patients with these conditions should undergo frequent medical examinations, which should include chest radiography and cytologic examination of the sputum. The present patient is a 47-year-old-man with PPK who suffered from metastatic non-small-cell carcinoma of the lung.

Carcinoma, Non-Small-Cell Lung↗
PubMed2025

Clinical and Genetic Findings in Patients With Palmoplantar Keratoderma.

IMPORTANCE: Palmoplantar keratoderma poses diagnostic challenges due to its clinical and genetic heterogeneity, and knowledge on the value of systematic genetic testing on clinically well-described patient cohorts is sparse. OBJECTIVE: To improve knowledge of the clinical and genetic spectrum of patients with palmoplantar keratoderma. DESIGN, SETTING, AND PARTICIPANTS: This cohort study prospectively recruited patients and affected family members with palmoplantar keratoderma between September 1, 2016, and December 31, 2022. Patients were recruited from private practitioners in dermatology and dermatology departments in Denmark. Study participants were patients 18 years or older either newly diagnosed with palmoplantar keratoderma or being followed up for the disease at referral centers. MAIN OUTCOMES AND MEASURES: Phenotypes and clinical subtypes were classified. Genetic testing was performed by whole-exome or genome sequencing using an in silico panel containing genes related to palmoplantar keratoderma, or by Sanger sequencing for specific variants. Descriptive analysis, such as proportions and frequency, were used to describe clinical characteristics, distribution of disease-causing variants, and genotype-phenotype associations. RESULTS: This study included 142 study participants from 76 families (90 [63%] female; median [range] age, 52 [18-92] years). Clinical subtypes included 42 punctate (55%), 26 diffuse (34%), 5 focal (7%), and 3 striate (4%). A genetic diagnosis was found in 63 of 76 families (83%), including 27 disease-causing variants within 13 different genes: AAGAB (n = 39), DSG1 (n = 8), KRT1 (n = 3), DSP (n = 2), KRT9 (n = 2), AQP5 (n = 2), KRT16 (n = 1), SERPINA12 (n = 1), ABCA12 (n = 1), COL7A1 (n = 1), CARD14 (n = 1), DST (n = 1), and LORICRIN (n = 1). All participants with AAGAB variants presented with punctate palmoplantar keratoderma, showing a clear genotype-phenotype correlation. The other subtypes (diffuse, focal, and striate) proved more challenging to clinically subclassify, and disease-causing variants were identified in 12 genes, contributing to more complex genotype-phenotype patterns. Patients with palmoplantar keratoderma due to DSP variants were found, which is important to identify because of an associated risk of cardiomyopathy. CONCLUSION AND RELEVANCE: This study provides novel insights into the clinical and genetic spectrum of patients with palmoplantar keratoderma. It demonstrates the value of genetic testing for accurate diagnoses and to distinguish between different subtypes. The established and well-described cohort lays the foundation for future research in palmoplantar keratoderma.

Humans↗
PubMedDate not supplied

Keratin 9 mutations in the coil 1A region in epidermolytic palmoplantar keratoderma.

The palmoplantar keratodermas (PPK) are a heterogeneous group of conditions, most frequently inherited in autosomal dominant fashion. A few are well-documented autosomal recessive disorders; other are acquired in association with certain metabolic disorders and malignancies. Recently different point mutations of the keratin 9 (K9) gene have been identified in unrelated families with epidermolytic palmoplantar keratoderma (EPPK). We investigated two unrelated Hungarian families with EPPK. In one, a mutation consisting of a G-->A transversion at nucleotide position 551, which changes codon arginine to glutamine at codon 162 (R162Q), was found. In the other, we observed a novel mutation at nucleotide position 571, which changes codon 169 lysine (AAG) into the amber stop codon (TAG) (K169X). Each found mutation is present in the highly conserved coil 1A region of the rod domain. In the case of a stop codon type of mutation, it is questionable whether it really results in a clinical phenotype, but segregation analysis revealed cosegregation of the PPK phenotype with the mutant allele.

Adult↗
PubMed1995

Mutations in the 1A domain of keratin 9 in patients with epidermolytic palmoplantar keratoderma.

Epidermolytic palmoplantar keratoderma is an autosomal dominant skin disorder characterized by hyperkeratosis of the palms and soles. Ultrastructurally the disease exhibits abnormal keratin filament networks and tonofilament clumping like that found in the keratin disorders of epidermolysis bullosa simplex and epidermolytic hyperkeratosis. The disease has been mapped to chromosome 17q11-q23 in the region of the type 1 keratin gene locus and more recently mutations have been found in the palmoplantar specific keratin, keratin 9. We have analyzed six unrelated incidences of epidermolytic palmoplantar keratoderma for mutations in their keratin 9 genes. In two of these, we have identified mutations that alter critical residues within the highly conserved helix initiation motif at the beginning of the rod domain of keratin 9. In a three-generation Middle Eastern kindred we found a C to T transition at codon 162 that results in an arginine to tryptophan substitution at position 10 of the 1A alpha-helical domain, thus confirming this codon as a hot spot for mutation in keratin 9. The other mutation found involves a T to C transition at codon 167 that results in the expression of a serine residue in place of the normal leucine at position 15 of the 1A segment and is the first documentation of this mutation in this gene. The identification of these substitutions extends the current catalog of disease causing mutations in keratin 9.

Base Sequence↗
PubMed2004

A novel mutation of keratin 9 gene (R162P) in a Japanese family with epidermolytic palmoplantar keratoderma.

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant inherited skin disorder characterized by hyperkeratosis of the skin over the palms and soles. Mutations in keratin 9 gene (KRT9) have been demonstrated in EPPK. In this study, we screened a Japanese family with EPPK for KRT9 mutation by polymerase chain reaction amplification of genomic sequences, followed by heteroduplex analysis and direct nucleotide sequencing. The mutation consisted of a G-to-C transversion at codon 162 in exon 1, which was located in the hot spot of the mutations that have been reported previously (R162Q and R162W). However, the amino acid substitution was proline for arginine (R162P) in the 1A rod domain, the highly conserved helix initiation motif of keratin 9. Our result illustrates the repertoire of KRT9 mutation underlying the occurrence of EPPK in a Japanese family and is an important contribution to the investigation of the genotype/phenotype correlation.

Arginine↗
PubMed2001

Aquagenic palmoplantar keratoderma.

Aquagenic palmoplantar keratoderma is an acquired condition characterized by burning and edema limited to the hands after brief immersion in water. The 3 patients described possess a striking similarity to those with transient reactive papulotranslucent acrokeratoderma. All 3 patients manifested the "hand-in-the-bucket" sign, having presented to a physician with a hand immersed in a bucket of water to more promptly demonstrate the physical findings. Aluminum chloride hexahydrate represents a potentially valuable therapeutic option for this unusual condition.

Adolescent↗
PubMed2004

A novel keratin 9 gene mutation (Asn160His) in a Taiwanese family with epidermolytic palmoplantar keratoderma.

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant inherited disorder of keratinization. Recent molecular studies have shown that EPPK is caused by mutations in keratin 9 gene (KRT9). We report a Taiwanese family with EPPK with a novel mutation with an A-->C transition at the first nucleotide of codon 160 in KRT9. The mutation is predicted to result in an asparagine to histidine substitution (N160H) at the beginning of the alpha-helical 1A domain of keratin 9. Mutations in this region could disrupt keratin filament assembly, leading to degeneration or cytolysis of keratinocytes. Our mutation analysis confirms that codon 160 in KRT9 is one of the mutation hot spots in EPPK.

Adult↗
PubMed2003

De novo mutation of keratin 9 gene in two Taiwanese patients with epidermolytic palmoplantar keratoderma.

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant hereditary disorder of keratinization. Recent molecular studies have shown that EPPK is caused by mutations in keratin 9 gene (K9). We report 2 unrelated sporadic cases of EPPK in Taiwanese, confirmed by histopathology and electron microscopy. A de novo mutation with a C to T transition at the first nucleotide of codon 162 in K9 was detected in both patients, but not in their parents. The mutation is expected to result in an arginine to tryptophan substitution (R162W) in the beginning region of the alpha-helical 1A domain of K9. Mutations in this region could disrupt keratin filament assembly, leading to degeneration or cytolysis of keratinocytes. Mutations of this arginine codon (R162W, R162Q) are common in pedigrees with EPPK. Our mutation analysis suggests that codon 162 in K9 gene is an important hot spot for mutation in EPPK.

Adult↗
PubMed1996

Linkage of an American pedigree with palmoplantar keratoderma and malignancy (palmoplantar ectodermal dysplasia type III) to 17q24. Literature survey and proposed updated classification of the keratodermas.

OBJECTIVES: To determine linkage in a pedigree with palmoplantar keratoderma (PPK) associated with squamous cell carcinoma of the esophagus. DESIGN: A large American pedigree was studied and the clinical phenotype was described. Linkage analysis was performed using genomic DNA from key individuals. SETTING: A community-based family study. PATIENTS: The family pedigree was expanded from a single index case. MAIN OUTCOME MEASURES: To demonstrate linkage and the relative risk of squamous cell carcinoma of the esophagus in this pedigree. RESULTS: Focal PPK was inherited as an autosomal dominant with variable expression, but signs were not limited to the palmoplantar epidermis. The generalized nature of this pattern of PPK was highlighted by the perifollicular papules and oral hyperkeratosis. Affected individuals (125 individuals) in 7 generations were identified, with 17 affected individuals having associated cancer. Seven of the 8 squamous cell carcinomas of the esophagus occurred in smokers. Other tumors were seen in nonsmokers, but these were not significantly increased. The combined male-female expected incidence of squamous cell carcinoma of the mouth and esophagus was 0.21; observed, 8 (relative risk of 38; P < .001). Linkage to the tylosis and esophageal cancer gene locus on 17q24 was demonstrated with a maximum 2-point lod score of 8.20 at zero recombination fraction for the DNA marker D17S1603. CONCLUSION: The distinctive clinical phenotype in this family suggests a new classification for PPKs, in particular a reappraisal of the phenotype as a focal PPK. A very similar phenotype is found in patients with keratin K16 gene mutations.

Chromosomes, Human, Pair 17↗
PubMed1999

A case of spontaneous mutation in the keratin 9 gene associated with epidermolytic palmoplantar keratoderma.

Epidermolytic palmoplantar keratoderma appears to be due to defects in keratin 9, the palmoplantar specific type 1 keratin. We report a case of spontaneous mutation, a C to T transition at codon 162, resulting in an arginine to tryptophan substitution in the 1 A region of the alpha helical rod domain of keratin 9. This provides further evidence that this codon is an important spot for mutation in keratin 9.

Child, Preschool↗
PubMed2003

Keratin 9 gene mutations in five Korean families with epidermolytic palmoplantar keratoderma.

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant disease characterized clinically by localized palmoplantar thickening and histopathologically by granular degeneration of the epidermis. Recent molecular biological studies have revealed that EPPK is caused by mutations of the keratin 9 gene in sequences mainly encoding the highly conserved 1 A rod domain. Here we demonstrate a novel mutation of N160H (position 8 of the 1 A domain) and two other previously reported mutations, R162W and N160S, in five unrelated Korean families with EPPK. The three-dimensional structure of the 1 A domain of the related vimentin intermediate filament protein chain is now known. Based on its likely similarity to the keratin 9 chain, we predict that inappropriate amino acid substitutions in position 10 of 1 A will likely interfere with coiled-coil dimer stability, and those in position 8 will interfere with tetramer stability. Accordingly, these mutations compromise the structural integrity of the keratin intermediate filaments leading to the pathology of EPPK.

Adolescent↗
PubMed1988

Epidermolytic palmoplantar keratoderma of Vörner: is it the most frequent type of hereditary palmoplantar keratoderma?

In a retrospective study, we reevaluated the biopsies that had been obtained, during the past 11 years, from 26 patients presenting with hereditary palmoplantar keratoderma (PPK). Twelve out of 26 biopsies disclosed the histological features of epidermolytic hyperkeratosis, consistent with the diagnosis of epidermolytic PPK of Vörner. A review of the histologically examined cases of the literature revealed a comparable predominance of this hereditary PPK. We conclude that, in contrast to the current opinion, epidermolytic PPK of Vörner represents the most frequent type of hereditary PPK.

Child, Preschool↗
PubMedDate not supplied

Identification of the keratin K9 R162W mutation in patients of Italian origin with epidermolytic palmoplantar keratoderma.

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant skin disorder characterized by hyperkeratosis of the palms and soles associated with histologic findings of hyperkeratosis and epidermolysis. Ultrastructurally, there is vacuolization of the cytoplasm and abnormal keratin filament network with tonofilament clumping. EPPK is caused by mutations in the keratin 9 gene (KRT9), which is expressed exclusively in suprabasal keratinocytes of palmoplantar epidermis. The mutation R162W is the most frequent keratin 9 alteration reported in patients from different geographical areas. We present three unrelated Italian families affected by EPPK in which we confirmed the presence of the R162W mutation, by RT-PCR analysis followed by sequencing of the KRT9 gene, in all affected members. The finding of the same mutation in all patients, together with the previous reports of the disease, strongly suggest that position 162 of the KRT9 gene represents a mutation "hot-spot", probably due to the peculiarity of the sequence.

Adult↗
PubMedDate not supplied

Palmoplantar keratodermas.

The palmoplantar skin is a highly specialized tissue which is able to resist mechanical trauma and other physical stress. In recent years the more descriptive classification of keratodermas has switched to an exact molecular genetic view where gene functions are considered. Palmoplantar keratodermas can be separated in the following functional subgroups: disturbed gene fuctions in structural proteins (keratins), cornified envelope (loricrin, transglutaminase), cohesion (plakophilin, desmoplakin, desmoglein1), cell-to-cell communication (connexins), and transmembrane signal transduction (cathepsin C). This review intends to emphasize the typical clinical aspects and symptom complexes associated with palmoplantar keratodermas which enable the astute dermatologist to make a clinical diagnosis. In addition the molecular genetic knowledge on the topic is given which is necessary to confirm the clinical diagnosis.

Biopsy, Needle↗