Palmoplantar Keratoderma Type Research Articles

Differentiating Verruca Plana and Palmoplantar Keratoderma by Comparing Clinical Features

Background: Distinguishing verruca plana (VP) from certain types of palmoplantar keratoderma (PPK) can pose challenges as there are few prior investigations. Objective: This study aimed to enhance the differentiation between VP and PPK by analyzing their clinical characteristics. Methods: We conducted a retrospective study involving patients diagnosed with VP, or PPK based on biopsy results. Results: We identified 38 cases with VP/PPK-like lesions on their hands. Among them, ten (26.3%) were diagnosed with VP, while 15 (39.5%) were diagnosed with PPK. VP lesions predominantly manifested on the dorsum of the hand, whereas PPK was primarily observed on the palm, and dorsum. Erythematous, or brownish-colored lesions were more commonly associated with VP, while PPK lesions typically presented as flesh-colored. Conclusion: By comparing the clinical distinctions between VP, and PPK, we aim to provide valuable insights to facilitate the differentiation of these two conditions, which can sometimes be diagnostically challenging.

Nadir Bir Olgu; Fokal Akral Hiperkeratoz

Focal acral hyperkeratosis (FAH) is a rare genodermatosis. FAH is usually observed in the second or third decades of life, and it is a type of palmoplantar keratoderma, a heterogeneous group of diseases characterized by abnormal incrassation of the palms and soles. Although it is an autosomal dominant inher- itance, it could also be sporadic. It is also known as a rare variant of Costa’s Acrokeratoelastoidosis (AKE). Its etiology is not known clearly and there is no effective treatment. In the present study, a 43-year-old recently diagnosed FAH case is presented due to its rarity and frequent confusion with AKE based on current literature.

Oligomer-to-monomer transition underlies the chaperone function of AAGAB in AP1/AP2 assembly

Assembly of protein complexes is facilitated by assembly chaperones. Alpha and gamma adaptin-binding protein (AAGAB) is a chaperone governing the assembly of the heterotetrameric adaptor complexes 1 and 2 (AP1 and AP2) involved in clathrin-mediated membrane trafficking. Here, we found that before AP1/2 binding, AAGAB exists as a homodimer. AAGAB dimerization is mediated by its C-terminal domain (CTD), which is critical for AAGAB stability and is missing in mutant proteins found in patients with the skin disease punctate palmoplantar keratoderma type 1 (PPKP1). We solved the crystal structure of the dimerization-mediating CTD, revealing an antiparallel dimer of bent helices. Interestingly, AAGAB uses the same CTD to recognize and stabilize the γ subunit in the AP1 complex and the α subunit in the AP2 complex, forming binary complexes containing only one copy of AAGAB. These findings demonstrate a dual role of CTD in stabilizing resting AAGAB and binding to substrates, providing a molecular explanation for disease-causing AAGAB mutations. The oligomerization state transition mechanism may also underlie the functions of other assembly chaperones.

Neoplasia-related spiny keratoderma: Dermoscopic findings of two cases and a literature review.

Neoplasia-related spiny keratoderma: Dermoscopic findings of two cases and a literature review.

A rare case of Vohwinkel’s syndrome

Keratoderma hereditarium mutilans or Vohwinkel’s syndrome is a rare autosomal dominant type of palmoplantar keratoderma characterized by honeycomb appearance, pseudoainhum leading to auto-amputation and stellate keratosis on knuckles. It’s mode of inheritance is autosomal dominant with mutation in loricrin and connexin 26 genes. We report the case of a 35-year-old female with alopecia universalis since birth and transgradient palmoplantar keratoderma, impaired hearing and pseudoainhum formation since childhood. This case is being reported to highlight the association of Vohwinkel’s syndrome with sensorineural hearing loss and alopecia universalis.

Palmoplantar hyperkeratotic projections

Palmoplantar hyperkeratotic projections

A clinico-epidemiological study of various keratinization disorders

<p class="abstract"><strong>Background:</strong> There is a vast spectrum of disorders with basic defect in the process of keratinization. There are various associations (genetic, autoimmune and environmental) with different keratinization disorders. The aims and objectives of this study to study the epidemiology, clinical features and associations in various keratinization disorders. </p><p class="abstract"><strong>Methods:</strong> A retrospective observational study of 500 patients was done in a tertiary care center. Detailed history was taken and clinical examination was done. Investigations and skin biopsy were performed when needed.<strong></strong></p><p class="abstract"><strong>Results:</strong> In our study of 500 cases of keratinizing disorders, there were 269 (53.8%) cases of psoriasis, 132 (26.4%) cases of palmoplantar keratoderma, 22 (4%) cases of phrynoderma, 19 (3.8%) cases of ichthyosis, 13 (2.6%) cases of acanthosis nigricans, 11 (2.2%) cases of porokeratosis, 7 (1.4%) cases of Darier’s disease, 3 (0.6%) Cases of pityriasis rubra pilaris, 2 (0.4%) cases each of pachyonychia congenita and erythron keratoderma. The most common age group affected was 51-60 years (19.6%). Males to female ratio was 1.13:1. Chronic plaque psoriasis (43.51%) was the most common variant of psoriasis. Psoriasis vulgaris (75%) was the most common cause of erythroderma. Histopathological findings in all patients whose biopsy was taken was consistent with clinical diagnosis. Non trans gradient (97.75%) was the most common type of palmoplantar keratoderma. Ichthyosis vulgaris (47.38%) was the most common type of ichthyosis.</p><p class="abstract"><strong>Conclusions:</strong> Heredity plays an important role in keratinization disorders. Also, various comorbidities have been associated with different keratinization disorders. Hence, we need to look for these factors while evaluating the patients of keratinization disorders.</p>

The C‐terminal Domain of AAGAB Mediates Tetramerization and Stability

In clathrin‐mediated endocytosis (CME), the coat protein clathrin relies on cargo adaptors such as the heterotetrameric AP2 adaptor complex to recruit cargo proteins to endocytic sites. It was previously thought that multimeric cargo adaptors such as AP2 adaptor assemble spontaneously. However, we recently discovered that AP2 adaptor assembly is an ordered process controlled by alpha and gamma adaptin binding protein (AAGAB). Without the assistance of AAGAB, AP2 adaptor fails to form, leading to CME defects. Heterozygous AAGAB mutations cause human diseases such as puncate palmoplantar keratoderma type 1 (PPKP1), a skin disorder characterized by lesions on palms and soles. However, the biochemical property and structure of AAGAB remain to be established. AAGAB is a soluble protein with two conserved regions – an N‐terminal G protein‐like domain (G domain) and a C‐terminal domain not similar to any known protein domain. We found that the full‐length AAGAB exists entirely as a homotetramer in solution and the tetramerization is mediated by its C‐terminal domain. Using X‐ray crystallography, we solved the atomic structure of the C‐terminal tetramerization domain (TD). The structure unveiled that the TD tetramer is formed by dimerization of two dimers. Furthermore, we observed that the expression level of the TD‐deficient AAGAB mutant (AAGABdeltaTD) in cells was drastically reduced compared to full‐length AAGAB. Together, our findings demonstrated that the TD mediates AAGAB tetramerization and is required for the stability of free AAGAB proteins prior to AP2 binding. These data also provide the first molecular explanation for the disease‐causing nonsense mutations found on AAGAB lacking the C‐terminal tetramerization domain.Support or Funding InformationFlorida State University startup funds to Yin; NIH/NIDDK R56 DK095367 to Shen; NIH/NIAID R21 AI128443 to Shen and Li.

AAGAB Mutations in 18 Canadian Families With Punctate Palmoplantar Keratoderma and a Possible Link to Cancer.

Punctate palmoplantar keratoderma type 1 (PPPK1) presents in late childhood to adulthood with multiple small discrete hyperkeratotic papules on palms and soles. PPPK1 is an autosomal dominant skin disease caused by AAGAB mutations. It has been suggested that PPPK1 may be associated with an increased predisposition to systemic malignancies. To evaluate the presence of AAGAB mutations in Canadian families with PPPK1 and the possible increased predisposition to systemic malignancies. Eighteen unrelated Canadian families with PPPK1 were recruited for this study. Genomic DNA was extracted from saliva and PCR amplification was performed for all AAGAB exons and exon/intron junctions. PCR products were sequenced and analyzed for mutations. A family history of malignancy was obtained from the index case and, when possible, from other family members. We have identified 5 heterozygous AAGAB loss of function mutations in 11 families. The mutation c.370 C>T, p.Arg124* was the most prevalent and was identified in 6 families. A splice site mutation, c.451+3delAAGT, was identified in 2 families. The other mutations c.473delG, p.Gly158Glufs*0; c.550-551insAAT, p.Gly183*; and c.505-506 dupAA, p.Asn169Lysfs*6 were each identified in 1 family. Different cancers were reported in 11 families (Table 1 and Supplemental Figure S1). AAGAB mutations were found in 11 of 18 families with PPPK1. In some families there appears to be an association with cancer.

AAGAB Controls AP2 Adaptor Assembly in Clathrin-Mediated Endocytosis

Multimeric adaptors are broadly involved in vesicle-mediated membrane trafficking. AP2 adaptor, in particular, plays a central role in clathrin-mediated endocytosis (CME) by recruiting cargo and clathrin to endocytic sites. It is generally thought that trafficking adaptors such as AP2 adaptor assemble spontaneously. In this work, however, we discovered that AP2 adaptor assembly is an ordered process controlled by alpha and gamma adaptin binding protein (AAGAB), an uncharacterized factor identified in our genome-wide genetic screen of CME. AAGAB guides the sequential association of AP2 subunits and stabilizes assembly intermediates. Without the assistance of AAGAB, AP2 subunits fail to form the adaptor complex, leading to their degradation. The function of AAGAB is abrogated by a mutation that causes punctate palmoplantar keratoderma type 1 (PPKP1), a human skin disease. Since other multimeric trafficking adaptors operate in an analogous manner to AP2 adaptor, their assembly likely involves a similar regulatory mechanism.

Excessive Punctate Palmoplantar Keratoderma Type 1 Lesions in a Patient Accompanied with Renal Failure

Excessive Punctate Palmoplantar Keratoderma Type 1 Lesions in a Patient Accompanied with Renal Failure

Clathrin Adaptor Complex-interacting Protein Irc6 Functions through the Conserved C-Terminal Domain

Clathrin coats drive transport vesicle formation from the plasma membrane and in pathways between the trans-Golgi network (TGN) and endosomes. Clathrin adaptors play central roles orchestrating assembly of clathrin coats. The yeast clathrin adaptor-interacting protein Irc6 is an orthologue of human p34, which is mutated in the inherited skin disorder punctate palmoplantar keratoderma type I. Irc6 and p34 bind to clathrin adaptor complexes AP-1 and AP-2 and are members of a conserved family characterized by a two-domain architecture. Irc6 is required for AP-1-dependent transport between the TGN and endosomes in yeast. Here we present evidence that the C-terminal two amino acids of Irc6 are required for AP-1 binding and transport function. Additionally, like the C-terminal domain, the N-terminal domain when overexpressed partially restores AP-1-mediated transport in cells lacking full-length Irc6. These findings support a functional role for Irc6 binding to AP-1. Negative genetic interactions with irc6∆ are enriched for genes related to membrane traffic and nuclear processes, consistent with diverse cellular roles for Irc6.

Mutations in AAGAB underlie autosomal dominant punctate palmoplantar keratoderma

Punctate palmoplantar keratoderma type 1 (PPPK1) is a rare autosomal dominant inherited skin disease, characterized by multiple hyperkeratotic lesions on the palms and soles. The causative gene for PPPK1 has been identified as AAGAB, which encodes α- and γ-adaptin-binding protein p34. We describe the clinical features in three unrelated families with PPPK1, and report three recurrent causative mutations in AAGAB.

Clinical and molecular investigation of Buschke‐Fischer‐Brauer in consanguineous Tunisian families

Punctate palmoplantar keratoderma type I (PPPK-BFB), also called Buschke-Fischer-Brauer disease (MIM 148600) is a rare autosomal dominant disorder of keratinization, characterized by multiple hyperkeratotic lesions on the palms and soles. Recently, PPPK-BFB has been shown to be associated with mutations in the AAGAB gene in several families of European, African, Canadian and Asian origins. To characterize the clinical and genetic features of PPPK-BFB in a broad group of Tunisian patients. Epidemiological and clinical data were collected from 18 PPPK-BFB patients belonging to eight Tunisian families. We carried out mutational and structural analysis for families not previously investigated. Sequencing of the remaining families identified a total of three different mutations in AAGAB gene: one founder mutation (c.348_349delAG, p.R116Sfs*1) specific to the inbred Tunisian population, one recurrent mutation and (c.370C>T, p.R124*) one novel variant (c.430C>G, p.E144K). This novel mutation, involving a conserved amino acid, is predicted to be probably damaging to the p34 protein function. Assessment of the phenotypic presentation of this group of Tunisian patients was marked by variable severity and varying age at onset with a possible presence of anticipation noted in five out of eight families (62.5%). There is no apparent genotype-phenotype correlation. Despite the high degree of inbreeding, no homozygous individuals for AAGAB mutations were observed. Homozygous carriers in AAGAB gene are likely non-viable. This study contributes to further characterize PPPK-BFB in consanguineous families and to extend the mutational spectrum of AAGAB gene in the Tunisian population.

Eight Novel Mutations Confirm the Role of AAGAB in Punctate Palmoplantar Keratoderma Type 1 (Buschke-Fischer-Brauer) and Show Broad Phenotypic Variability.

Punctate palmoplantar keratoderma (PPKP1; Buschke-Fischer-Brauer) is a rare autosomal dominant inherited skin disease characterized by multiple hyperkeratotic papules involving the palms and soles. Mutations have been found at 2 loci, on chromosomes 15q22-15q24 and 8q24.13-8q24.21. We recently identified mutations in 3 families, in the AAGAB gene on 15q, which encodes the alpha- and gamma-adaptin-binding protein p34. The current study examined 14 additional families, comprising a total of 26 affected individuals and identified 8 novel mutations in 9 families. In one family a mutation that was present only in the affected individuals was found, and in 4 other families, previously reported mutations were found (1, 2). These results confirm the role of AAGAB in PPKP1. Our findings suggest that there is no correlation with age, but with mechanical factors. No additional obvious genotype-phenotype correlation was observed, even when comparing different types of mutations. Rather, identical genotypes presented a very broad interfamilial and intrafamilial variability of phenotypes.

Keratoderma hereditarium mutilans (Vohwinkel′s syndrome)

Vohwinkel's syndrome is an autosomal dominant type of palmoplantar keratoderma characterized by honeycomb appearance, pseudoainhum leading to autoamputation, stellate keratosis on knuckles, and associated with sensorineural deafness.An Ichthyotic variant is recently described .We report a rare case of Vohwinkels syndrome with ichthyosis.

Punctate Palmoplantar Keratoderma Type 1: A Novel AAGAB Mutation and Efficacy of Etretinate

Punctate Palmoplantar Keratoderma Type 1: A Novel AAGAB Mutation and Efficacy of Etretinate

New and recurrent AAGAB mutations in punctate palmoplantar keratoderma

New and recurrent <i> <scp>AAGAB</scp> </i> mutations in punctate palmoplantar keratoderma

Keratoderma, hypotrichosis and leukonychia totalis: a new syndrome?

We report three members of a family with congenital hypotrichosis, characterized by trichorrhexis nodosa and trichoptilosis, dry skin, keratosis pilaris and leukonychia totalis. They also developed a progressive transgrediens type of palmoplantar keratoderma, and hyperkeratotic lesions on the knees, elbows and perianal region. As far as we are aware, this combination of clinical features has not been described previously.

Palmoplantar keratoderma and associated syndromes

This article focuses on the current state of knowledge concerning the characterization and classification of palmoplantar keratoderma and associated syndromes. In addition, therapeutic options are discussed. Exact diagnosis enables dermatologists to give patients accurate genetic counseling and may help to detect underlying defects or proneness to cancer. Furthermore, precise classification of this disease facilitates the use of the most efficient therapeutic modalities. Important criteria for the classification of palmoplantar keratoderma are the mode of transmission, age at onset, and distribution of the keratoderma. The disorder may be diffuse or focal; it may be restricted to the palms and soles or also involve the dorsal aspects of the hands and feet. Psoriatic-like lesions in other parts of the body may occur in certain variants. The association of other signs and symptoms may provide diagnostic clues. Ultrastructural investigation will show diagnostic features in some types of palmoplantar keratoderma, and biochemical analysis may be helpful in the classification of keratoderma. In the future, the most accurate diagnosis will be the identification of the genetic defect and its chromosomal localization.