78 results on '"Keratoderma, Palmoplantar, Diffuse genetics"'
Search Results
2. Novel mutations in desmoglein 1: focal palmoplantar keratoderma in milder phenotypes.
- Author
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Zamiri M, Wilson NJ, O'Toole EA, and Smith FJD
- Subjects
- Adult, DNA Mutational Analysis, Female, Humans, Keratoderma, Palmoplantar, Diffuse diagnosis, Male, Mutation, Papilloma diagnosis, Pedigree, Desmoglein 1 genetics, Keratoderma, Palmoplantar, Diffuse genetics, Papilloma genetics
- Published
- 2019
- Full Text
- View/download PDF
3. Japanese case of Bothnian-type palmoplantar keratoderma with a novel missense mutation of p.Trp35Ser in extracellular loop A of aquaporin-5.
- Author
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Wada Y, Kusakabe M, Nagai M, Imai Y, and Yamanishi K
- Subjects
- Adult, DNA Mutational Analysis, Humans, Japan, Keratoderma, Palmoplantar, Diffuse diagnosis, Keratoderma, Palmoplantar, Diffuse pathology, Male, Mutation, Missense, Skin pathology, Aquaporin 5 genetics, Keratoderma, Palmoplantar, Diffuse genetics
- Published
- 2019
- Full Text
- View/download PDF
4. Palmoplantar keratoderma Bothnia type with acrokeratoelastoidosis-like features due to AQP5 mutations.
- Author
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Pan Y, Men Y, and Lin Z
- Subjects
- Asian People, Biopsy, Child, Preschool, China, DNA Mutational Analysis, Female, Humans, Infant, Keratoderma, Palmoplantar, Diffuse pathology, Male, Pedigree, Skin pathology, Aquaporin 5 genetics, Gain of Function Mutation, Keratoderma, Palmoplantar, Diffuse genetics
- Published
- 2019
- Full Text
- View/download PDF
5. Palmoplantar Hyperkeratosis and Strong Family History of Esophageal Cancer: Tylosis or Not?
- Author
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Abidali H, Muna-Aguon P, Vela S, and Nanda R
- Subjects
- Barrett Esophagus genetics, Barrett Esophagus pathology, Biopsy, Carrier Proteins genetics, Endoscopy, Digestive System, Esophageal Neoplasms genetics, Esophageal Neoplasms pathology, Esophagus diagnostic imaging, Esophagus pathology, Humans, Intracellular Signaling Peptides and Proteins, Keratoderma, Palmoplantar, Diffuse genetics, Keratoderma, Palmoplantar, Diffuse pathology, Male, Middle Aged, Pedigree, Watchful Waiting, Barrett Esophagus diagnostic imaging, Esophageal Neoplasms diagnosis, Keratoderma, Palmoplantar, Diffuse diagnosis, Medical History Taking
- Published
- 2018
- Full Text
- View/download PDF
6. A novel heterozygous missense mutation of the desmoglein 1 gene in a Chinese family with diffuse nonepidermolytic palmoplantar keratoderma.
- Author
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Wang D, He Y, and Wang S
- Subjects
- Female, Foot pathology, Hand pathology, Humans, Male, Middle Aged, Pedigree, Asian People genetics, Desmoglein 1 genetics, Heterozygote, Keratoderma, Palmoplantar, Diffuse diagnosis, Keratoderma, Palmoplantar, Diffuse genetics, Mutation, Missense genetics
- Abstract
Competing Interests: There are no conflicts of interest
- Published
- 2018
- Full Text
- View/download PDF
7. Tissue-specific role of RHBDF2 in cutaneous wound healing and hyperproliferative skin disease.
- Author
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Hosur V, Lyons BL, Burzenski LM, and Shultz LD
- Subjects
- Animals, Bone Marrow Transplantation, Cell Proliferation genetics, Disease Models, Animal, Mice, Mice, Congenic, Mice, Inbred C57BL, Mice, Inbred MRL lpr, Phenotype, Carrier Proteins physiology, Keratinocytes, Keratoderma, Palmoplantar, Diffuse genetics, Skin Transplantation, Wound Healing genetics
- Abstract
Objective: Gain-of-function (GOF) mutations in RHBDF2 cause tylosis. Patients present with hyperproliferative skin, and keratinocytes from tylosis patients' skin show an enhanced wound-healing phenotype. The curly bare mouse model of tylosis, carrying a GOF mutation in the Rhbdf2 gene (Rhbdf2
cub ), presents with epidermal hyperplasia and shows accelerated cutaneous wound-healing phenotype through enhanced secretion of the epidermal growth factor receptor family ligand amphiregulin. Despite these advances in our understanding of tylosis, key questions remain. For instance, it is not known whether the disease is skin-specific, whether the immune system or the surrounding microenvironment plays a role, and whether mouse genetic background influences the hyperproliferative-skin and wound-healing phenotypes observed in Rhbdf2cub mice., Results: We performed bone marrow transfers and reciprocal skin transplants and found that bone marrow transfer from C57BL/6 (B6)-Rhbdf2cub/cub donor mice to B6 wildtype recipient mice failed to transfer the hyperproliferative-skin and wound-healing phenotypes in B6 mice. Furthermore, skin grafts from B6 mice to the dorsal skin of B6-Rhbdf2cub/cub mice maintained the phenotype of the donor mice. To test the influence of mouse genetic background, we backcrossed Rhbdf2cub onto the MRL/MpJ strain and found that the hyperproliferative-skin and wound-healing phenotypes caused by the Rhbdf2cub mutation persisted on the MRL/MpJ strain.- Published
- 2017
- Full Text
- View/download PDF
8. Autosomal dominant diffuse nonepidermolytic palmoplantar keratoderma due to a recurrent mutation in aquaporin-5.
- Author
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Abdul-Wahab A, Takeichi T, Liu L, Lomas D, Hughes B, Akiyama M, McGrath JA, and Mellerio JE
- Subjects
- Female, HapMap Project, Haplotypes, Humans, Male, Pedigree, Aquaporin 5 genetics, Keratoderma, Palmoplantar, Diffuse genetics, Mutation, Missense genetics, Polymorphism, Single Nucleotide genetics
- Published
- 2016
- Full Text
- View/download PDF
9. Functional Analysis of a Novel Connexin30 Mutation in a Large Family with Hearing Loss, Pesplanus, Ichthyosis, Cutaneous Nodules, and Keratoderma.
- Author
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Pandey N, Xavier DF, Chatterjee A, Mani RS, Hiremagalore R, Tharakan A, Rajashekhar B, and Anand A
- Subjects
- Biotin analogs & derivatives, Biotin metabolism, Connexin 30, DNA Mutational Analysis, Female, Genetic Linkage, Humans, Ichthyosis genetics, Keratoderma, Palmoplantar, Diffuse genetics, Male, Pedigree, Phenotype, Connexins genetics, Hearing Loss, Sensorineural genetics, Skin Diseases, Genetic genetics
- Abstract
Mutations in the gap-junction gene Cx30 (Connexin30, GJB6) are a known cause of hearing loss. Here, we report our findings on a large multigeneration family in which severe to profound sensorineural hearing impairment is associated with a variety of skin-related anomalies. Genome-wide analysis of the family showed that the locus maps to chromosome region 13ptel-q12.1 and that a novel mutation, p.N54K, in Cx30, cosegregates with the phenotype. Unlike wild-type Cx30, p.N54K Cx30 is predominantly localized in the cytoplasm and does not permit transfer of neurobiotin, suggesting improper cellular localization and abolishment of gap-junction activity., (© 2015 John Wiley & Sons Ltd/University College London.)
- Published
- 2016
- Full Text
- View/download PDF
10. Olmsted syndrome in an Indian male with a new de novo mutation in TRPV3.
- Author
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Agarwala MK, George R, Pramanik R, and McGrath JA
- Subjects
- Adult, Heterozygote, Humans, Male, Pedigree, Syndrome, Keratoderma, Palmoplantar, Diffuse genetics, Mutation genetics, TRPV Cation Channels genetics
- Published
- 2016
- Full Text
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11. Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms.
- Author
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Ellis A, Risk JM, Maruthappu T, and Kelsell DP
- Subjects
- Diagnosis, Differential, Esophageal Neoplasms therapy, Humans, Keratoderma, Palmoplantar, Diffuse therapy, Disease Management, Esophageal Neoplasms diagnosis, Esophageal Neoplasms genetics, Keratoderma, Palmoplantar, Diffuse diagnosis, Keratoderma, Palmoplantar, Diffuse genetics
- Abstract
Tylosis (hyperkeratosis palmaris et plantaris) is characterised by focal thickening of the skin of the hands and feet and is associated with a very high lifetime risk of developing squamous cell carcinoma of the oesophagus. This risk has been calculated to be 95% at the age of 65 in one large family, however the frequency of the disorder in the general population is not known and is likely to be less than one in 1,000,000. Oesophageal lesions appear as small (2-5 mm), white, polyploid lesions dotted throughout the oesophagus and oral leukokeratosis has also been described. Although symptoms of oesophageal cancer can include dysphagia, odynophagia, anorexia and weight loss, there may be an absence of symptoms in early disease, highlighting the importance of endoscopic surveillance in these patients. Oesophageal cancer associated with tylosis usually presents in middle to late life (from mid-fifties onwards) and shows no earlier development than the sporadic form of the disease. Tylosis with oesophageal cancer is inherited as an autosomal dominant trait with complete penetrance of the cutaneous features, usually by 7 to 8 years of age but can present as late as puberty. Mutations in RHBDF2 located on 17q25.1 have recently been found to be causative. A diagnosis of tylosis with oesophageal cancer is made on the basis of a positive family history, characteristic clinical features, including cutaneous and oesophageal lesions, and genetic analysis for mutations in RHBDF2. The key management goal is surveillance for early detection and treatment of oesophageal dysplasia. Surveillance includes annual gastroscopy with biopsy of any suspicious lesion together with quadratic biopsies from the upper, middle and lower oesophagus. This is coupled with dietary and lifestyle modification advice and symptom education. Symptomatic management of the palmoplantar keratoderma includes regular application of emollients, specialist footwear and early treatment of fissures and super-added infection, particularly tinea pedis. More specific treatment for the thick skin is available in the form of oral retinoids, which are very effective but commonly produce side effects, including nasal excoriation and bleeding, hypercholesterolaemia, and abnormal liver function tests. Genetic counselling can be offered to patients and family members once a family history has been established. The prognosis of tylosis with oesophageal cancer is difficult to determine due to the limited number of affected individuals. In the last 40 years of surveillance, five out of six cases of squamous oesophageal cancer in the Liverpool family were detected endoscopically and were surgically removed. Four of five patients had stage 1 disease at presentation and remain alive and well more than 8 years later. This suggests that the presence of a screening program improves prognosis for these patients.
- Published
- 2015
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12. A spontaneous KRT16 mutation in a dog breed: a model for human focal non-epidermolytic palmoplantar keratoderma (FNEPPK).
- Author
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Plassais J, Guaguère E, Lagoutte L, Guillory AS, de Citres CD, Degorce-Rubiales F, Delverdier M, Vaysse A, Quignon P, Bleuart C, Hitte C, Fautrel A, Kaerle C, Bellaud P, Bensignor E, Queney G, Bourrat E, Thomas A, and André C
- Subjects
- Animals, Disease Models, Animal, Dogs, Exons, Female, Humans, Immunoenzyme Techniques, Immunohistochemistry, Male, Microscopy, Fluorescence, RNA, Messenger metabolism, Real-Time Polymerase Chain Reaction, Species Specificity, Keratin-16 genetics, Keratoderma, Palmoplantar, Diffuse genetics, Mutation, Papilloma genetics
- Published
- 2015
- Full Text
- View/download PDF
13. Focal palmar keratoderma and leukokeratosis anogenitalis: an extremely rare genodermatosis associated with cytokeratine 17 mutation.
- Author
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Nantel-Battista M, Friedmann D, Kokta V, Bouffard D, and Funaro D
- Subjects
- Female, Humans, Keratoderma, Palmoplantar, Diffuse genetics, Leukoplakia genetics, Middle Aged, Papilloma genetics, Keratin-17 genetics, Keratoderma, Palmoplantar, Diffuse complications, Leukoplakia complications, Mutation, Papilloma complications
- Published
- 2015
- Full Text
- View/download PDF
14. A gain-of-function mutation in TRPV3 causes focal palmoplantar keratoderma in a Chinese family.
- Author
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He Y, Zeng K, Zhang X, Chen Q, Wu J, Li H, Zhou Y, Glusman G, Roach J, Etheridge A, Qing S, Tian Q, Lee I, Tian X, Wang X, Wu Z, Hood L, Ding Y, and Wang K
- Subjects
- Adult, Family, Humans, Keratoderma, Palmoplantar, Diffuse pathology, Male, Papilloma pathology, Phenotype, Skin pathology, Asian People genetics, Keratoderma, Palmoplantar, Diffuse genetics, Mutation genetics, Papilloma genetics, TRPV Cation Channels genetics
- Published
- 2015
- Full Text
- View/download PDF
15. Mutation p.Leu128Pro in the 1A domain of K16 causes pachyonychia congenita with focal palmoplantar keratoderma in a Chinese family.
- Author
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Dai L, Wu J, Guo H, Huang Y, Zhang K, Liu D, Fu L, Wu Y, Guan X, Bai Y, and Liao Q
- Subjects
- Adult, Child, Preschool, Female, Humans, Male, Pedigree, Phenotype, Asian People genetics, Keratin-16 genetics, Keratoderma, Palmoplantar, Diffuse genetics, Mutation, Missense, Pachyonychia Congenita genetics, Papilloma genetics
- Abstract
Unlabelled: Pachyonychia congenita (PC), a rare autosomal dominant disorder characterized by hypertrophic nail dystrophy, is classified into two main clinical subtypes: PC-1 and PC-2. PC-1 is associated with mutations in the KRT6A or KRT16 genes, whereas PC-2 is linked to KRT6B or KRT17 mutations. Blood samples were collected from three generations of a new Chinese PC-1 family, including three PC patients and five unaffected family members. A novel missense mutation p.Leu128Pro (c.383T>C) was identified in a highly conserved helix motif in domain 1A of K16. The disease haplotype carried the mutation and cosegregated with the affection status. PolyPhen2 and SIFTS analysis rated the substitution as probably damaging; Swiss-Model analysis indicated that the structure of the mutant protein contained an unnormal α-helix. Overexpression of mutant protein in cultured cells led to abnormal cell morphology., Conclusion: The wider spectrum of KRT16 mutations suggests that changes in codons 125, 127, and 132 are most commonly responsible for PC-1 and that proline substitution mutations at codons 127 or 128 may produce more severe disease. This study extends the KRT16 mutation spectrum and adds new information on the clinical and genetic diversity of PC.
- Published
- 2014
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16. Mutation in AQP5, encoding aquaporin 5, causes palmoplantar keratoderma Bothnia type.
- Author
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Cao X, Yin J, Wang H, Zhao J, Zhang J, Dai L, Zhang J, Jiang H, Lin Z, and Yang Y
- Subjects
- Adult, Family Health, Female, Humans, Male, Pedigree, Aquaporin 5 genetics, Asian People genetics, Keratoderma, Palmoplantar, Diffuse genetics
- Published
- 2014
- Full Text
- View/download PDF
17. Mutations in AQP5, encoding a water-channel protein, cause autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma.
- Author
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Blaydon DC, Lind LK, Plagnol V, Linton KJ, Smith FJ, Wilson NJ, McLean WH, Munro CS, South AP, Leigh IM, O'Toole EA, Lundström A, and Kelsell DP
- Subjects
- Base Sequence, Epidermis physiopathology, Genes, Dominant, Humans, Keratoderma, Palmoplantar, Diffuse physiopathology, Models, Molecular, Molecular Sequence Data, Pedigree, Protein Transport, Water metabolism, Aquaporin 5 genetics, Cell Membrane metabolism, Epidermis metabolism, Keratoderma, Palmoplantar, Diffuse genetics, Mutation, Wrist physiopathology
- Abstract
Autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma is characterized by the adoption of a white, spongy appearance of affected areas upon exposure to water. After exome sequencing, missense mutations were identified in AQP5, encoding water-channel protein aquaporin-5 (AQP5). Protein-structure analysis indicates that these AQP5 variants have the potential to elicit an effect on normal channel regulation. Immunofluorescence data reveal the presence of AQP5 at the plasma membrane in the stratum granulosum of both normal and affected palmar epidermis, indicating that the altered AQP5 proteins are trafficked in the normal manner. We demonstrate here a role for AQP5 in the palmoplantar epidermis and propose that the altered AQP5 proteins retain the ability to form open channels in the cell membrane and conduct water., (Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
18. [The perennial problem of keratinisation disorders].
- Author
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Dereure O
- Subjects
- Cations metabolism, Connexin 26, Connexins deficiency, Connexins genetics, Deafness genetics, Deafness pathology, Genes, Recessive, Humans, Ichthyosis genetics, Ichthyosis pathology, Ion Transport, Keratinocytes metabolism, Keratinocytes pathology, Keratins metabolism, Keratitis genetics, Keratitis pathology, Keratoderma, Palmoplantar genetics, Keratoderma, Palmoplantar pathology, Keratoderma, Palmoplantar, Diffuse genetics, Keratoderma, Palmoplantar, Diffuse pathology, Mosaicism, Nevus genetics, Porokeratosis genetics, Skin Diseases, Genetic pathology, Sweat Gland Neoplasms genetics, TRPV Cation Channels deficiency, TRPV Cation Channels genetics, Skin Diseases, Genetic genetics
- Published
- 2013
- Full Text
- View/download PDF
19. Diffuse epidermolytic palmoplantar keratoderma (Unna-Thost-).
- Author
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Hinterberger L, Pföhler C, Vogt T, and Müller CS
- Subjects
- Adult, Humans, Male, Keratins, Hair-Specific genetics, Keratins, Type II genetics, Keratoderma, Palmoplantar classification, Keratoderma, Palmoplantar genetics, Keratoderma, Palmoplantar, Diffuse classification, Keratoderma, Palmoplantar, Diffuse genetics, Keratoderma, Palmoplantar, Epidermolytic classification, Keratoderma, Palmoplantar, Epidermolytic genetics, Mutation, Skin pathology
- Published
- 2012
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20. Analysis of a Finnish family confirms RHBDF2 mutations as the underlying factor in tylosis with esophageal cancer.
- Author
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Saarinen S, Vahteristo P, Lehtonen R, Aittomäki K, Launonen V, Kiviluoto T, and Aaltonen LA
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Finland, Humans, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, Pedigree, Carrier Proteins genetics, Esophageal Neoplasms genetics, Keratoderma, Palmoplantar, Diffuse genetics, Mutation, Missense
- Abstract
Tylosis with esophageal cancer (TOC) is a rare familial cancer syndrome inherited in an autosomal-dominant manner and characterized by esophageal cancer susceptibility and hyperkeratotic skin lesions. Two heterozygous missense mutations in the RHBDF2 gene were recently reported to be associated with TOC in three families: a p.Ile186Thr mutation was found in families from the UK and the US and a p.Pro189Leu mutation was detected in a German TOC family. We aimed to validate these novel results in an independent material by screening RHBDF2 in a previously unreported Finnish TOC family. We identified a new missense mutation, p.Asp188Asn, segregating with TOC in the Finnish family, and interestingly the detected mutation alters a codon located between the two previously reported mutation sites. Thus, we confirmed RHBDF2 mutations as the underlying cause of the TOC syndrome and our results suggest that the TOC associated mutations might be specific for this particular site in the RHBDF2 gene. These results enable the genetic counseling and diagnostic mutation screening of the members of TOC families.
- Published
- 2012
- Full Text
- View/download PDF
21. [RHBDF2 mutations in familial palmoplantar keratoderma associated with tylosis oesophageal cancer].
- Author
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Dereure O
- Subjects
- Humans, Esophageal Neoplasms complications, Esophageal Neoplasms genetics, Keratoderma, Palmoplantar, Diffuse complications, Keratoderma, Palmoplantar, Diffuse genetics, Membrane Proteins genetics, Mutation
- Published
- 2012
- Full Text
- View/download PDF
22. Manifestation of diffuse yellowish keratoderma on the palms and soles in autosomal recessive congenital ichthyosis patients may be indicative of mutations in NIPAL4.
- Author
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Alavi A, Shahshahani MM, Klotzle B, Fan JB, Ronaghi M, and Elahi E
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Genes, Recessive, Genetic Association Studies, Humans, Ichthyosiform Erythroderma, Congenital complications, Iran, Keratoderma, Palmoplantar, Diffuse complications, Male, Mutation, Pedigree, Young Adult, Ichthyosiform Erythroderma, Congenital genetics, Ichthyosiform Erythroderma, Congenital pathology, Ichthyosis, Lamellar genetics, Ichthyosis, Lamellar pathology, Keratoderma, Palmoplantar, Diffuse genetics, Keratoderma, Palmoplantar, Diffuse pathology, Receptors, Cell Surface genetics
- Abstract
Ichthyosis is a heterogeneous disorder characterized by abnormal skin scaling over the whole body. Autosomal recessive congenital ichthyosis (ARCI) comprises various forms, the most important of which are lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). Seven genes have been identified to be causative of ARCI, and these account for disease in 60-80% of the patients. There is notable phenotypic overlap between the major forms of ARCI, and a strong genotype-phenotype correlation has not been found. Here, we initially aimed to identify the causative gene in a large Iranian ARCI pedigree, and subsequently performed genetic analysis on four other affected pedigrees. A genotype-phenotype correlation was sought. Whole genome homozygosity mapping using high-density single nucleotide polymorphism chips was performed on the large pedigree. Linkage to chromosome 5 and a mutation in NIPAL4 causing p.G297R were identified. The same mutation was also identified in two of the remaining four Iranian pedigrees. Two of the NIPAL4 mutation bearing pedigrees were classified as CIE and one as LI. Notably, all NIPAL4 mutation-bearing patients manifested diffuse yellowish keratoderma on the palms and soles. We provide evidence suggesting presentation of this diffuse yellowish keratoderma may be indicative of mutations in NIPAL4, providing an easily assessable genotype-phenotype correlation., (© 2011 Japanese Dermatological Association.)
- Published
- 2012
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- View/download PDF
23. RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome.
- Author
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Blaydon DC, Etheridge SL, Risk JM, Hennies HC, Gay LJ, Carroll R, Plagnol V, McRonald FE, Stevens HP, Spurr NK, Bishop DT, Ellis A, Jankowski J, Field JK, Leigh IM, South AP, and Kelsell DP
- Subjects
- Amino Acid Sequence, Carcinoma, Squamous Cell genetics, Cell Growth Processes genetics, Cell Movement genetics, Chromosomes, Human, Pair 17 genetics, ErbB Receptors genetics, Esophageal Neoplasms enzymology, Esophageal Neoplasms metabolism, Esophageal Neoplasms pathology, Exons, Humans, Keratinocytes metabolism, Keratoderma, Palmoplantar, Diffuse enzymology, Keratoderma, Palmoplantar, Diffuse metabolism, Keratoderma, Palmoplantar, Diffuse pathology, Molecular Sequence Data, Pedigree, Phenotype, Sequence Alignment, Serine Endopeptidases, Untranslated Regions, Esophageal Neoplasms genetics, Keratoderma, Palmoplantar, Diffuse genetics, Mutation, Missense, Serine Proteases genetics
- Abstract
Tylosis esophageal cancer (TOC) is an autosomal-dominant syndrome characterized by palmoplantar keratoderma, oral precursor lesions, and a high lifetime risk of esophageal cancer. We have previously localized the TOC locus to a small genomic interval within chromosomal region 17q25. Using a targeted capture array and next-generation sequencing, we have now identified missense mutations (c.557T>C [p.Ile186Thr] and c.566C>T [p.Pro189Leu] in RHBDF2, which encodes the inactive rhomboid protease RHBDF2 (also known as iRhom2), as the underlying cause of TOC. We show that the distribution of RHBDF2 in tylotic skin is altered in comparison with that in normal skin, and immortalized tylotic keratinocytes have decreased levels of total epidermal growth factor receptor (EGFR) and display an increased proliferative and migratory potential relative to normal cells, even when normal cells are stimulated with exogenous epidermal growth factor. It would thus appear that EGFR signaling is dysregulated in tylotic cells. Furthermore, we also show an altered localization of RHBDF2 in both tylotic and sporadic squamous esophageal tumors. The elucidation of a role of RHBDF2 in growth-factor signaling in esophageal cancer will help to determine whether targeting this pathway in chemotherapy for this and other squamous cell carcinomas will be effective., (Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
24. Tylosis A with squamous cell carcinoma of the oesophagus in a Spanish family.
- Author
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Varela AB, Blanco Rodríguez MM, Boullosa PE, and Silva JG
- Subjects
- Adult, Aged, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell radiotherapy, Carcinoma, Squamous Cell surgery, Child, Preschool, Chromosomes, Human, Pair 17 genetics, Esophageal Neoplasms genetics, Esophageal Neoplasms radiotherapy, Esophageal Neoplasms surgery, Female, Genetic Loci, Humans, Keratoderma, Palmoplantar, Diffuse genetics, Middle Aged, Spain, Young Adult, Carcinoma, Squamous Cell diagnosis, Esophageal Neoplasms diagnosis, Keratoderma, Palmoplantar, Diffuse diagnosis
- Abstract
Palmoplantar tylosis is a focal nonepidermolytic palmoplantar hyperkeratosis, which is inherited as an autosomal dominant condition. Two types have been described: an early onset type B tylosis, which occurs in the first year of life and is usually benign, and type A tylosis, which occurs between the ages of 5 and 15 years. Type A tylosis has been associated with a high incidence of oesophageal carcinoma in three families in England, Germany and the USA. This study describes an additional family from Spain with tylosis A, without any known relation to those described before.
- Published
- 2011
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25. [Clinical and genetic characteristics of Buschke-Fischer-Brauer's disease in a Tunisian family].
- Author
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El Amri I, Mamai O, Ghariani N, Denguezli M, Sriha B, Adala L, Saad A, Gribaa M, and Nouira R
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Chromosome Mapping, DNA genetics, Epidermis pathology, Female, Genes, Dominant, Haplotypes genetics, Humans, Keratoderma, Palmoplantar, Diffuse epidemiology, Keratoderma, Palmoplantar, Diffuse pathology, Lod Score, Male, Microsatellite Repeats, Middle Aged, Pedigree, Tunisia epidemiology, Chromosomes, Human, Pair 15 genetics, Keratoderma, Palmoplantar, Diffuse genetics
- Abstract
Background: Punctate palmoplantar keratoderma (PPPK), or Buschke-Fischer-Brauer's disease, is a rare form of genodermatosis with autosomal dominant transmission and with variable penetrance. Its molecular basis remains unknown. Two loci were found to be linked to this disease: one on 15q22 and the other on 8q24. We report the clinical and genetic characteristics of PPPK in a Tunisian family., Patients and Methods: A Tunisian family with PPPK was identified through a proband. As far as possible, history taking, physical examination, histopathological tests and blood sampling for DNA extraction were carried out for each patient., Results: Seventeen patients were included in this study. Age ranged from 15 to 81 years with a sex-ratio of 3.2 m/f. Lesions appeared between the ages of 10 and 65 years and at a mean of 28 years. Clinically, lesions ranged from few keratotic papules on the palms to coalescence of lesions in plaques over palmar and/or plantar surfaces. Hyperhydrosis, hypopigmented macules and nail dystrophy were frequently associated. In all patients, histopathological examination revealed thickening of the epidermis with compact orthohyperkeratosis overlying a small and sharply demarcated area of depressed epidermis. Mechanical measures and keratolytic ointments proved non-beneficial. Genotyping for chromosomes 8 and 15 as well as LOD scores confirmed genetic linkage with the suspected locus on chromosome 15q, with the interval of the locus in question reduced to 3.26 Mb. This region is flanked by markers D15S987 and D15S153., Conclusion: Our study of this family confirmed the classical characteristics of KPP-BFB as well as demonstrating several associated clinical signs of which the significance will be determined in subsequent studies. Further screening studies to identify mutated genes in the region of interest will help us to understand the molecular basis of this disease and hopefully to propose suitable treatment., (2010 Elsevier Masson SAS. All rights reserved.)
- Published
- 2010
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26. Ichthyosis hystrix Curth-Macklin type in an African girl.
- Author
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Yusuf SM, Mijinyawa MS, Maiyaki MB, and Mohammed AZ
- Subjects
- Adolescent, Female, Humans, Ichthyosis drug therapy, Ichthyosis genetics, Keratoderma, Palmoplantar, Diffuse drug therapy, Keratoderma, Palmoplantar, Diffuse genetics, Loss of Heterozygosity, Treatment Failure, Ichthyosis pathology, Keratoderma, Palmoplantar, Diffuse pathology
- Abstract
Ichthyosis hystrix Curth-Macklin type is a rare autosomal dominant skin disorder characterized by extensive hyperkeratosis and palmo-plantar keratoderma. It results from heterozygous frameshift mutation in keratin 1 gene (KRT1). Histological features, showing perinuclear vacuolization and binucleated cells, are similar to those of epidermolytic hyperkeratosis except for the absence of epidermolysis. The present report describes the condition in a 16-year-old African girl where available treatment was disappointing.
- Published
- 2009
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- View/download PDF
27. [Hereditary tylosis syndrome and esophagus cancer].
- Author
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de Souza CA, Santos Ada C, Santos Lda C, and Carneiro AL
- Subjects
- Adult, Female, Humans, Keratoderma, Palmoplantar, Diffuse genetics, Carcinoma, Squamous Cell complications, Esophageal Neoplasms complications, Keratoderma, Palmoplantar, Diffuse complications
- Abstract
Tylosis palmoplantaris is an autosomal dominant disorder characterized by hyperkeratosis of palms and soles. Lesions start during childhood and are more evident in areas of pressure. Familial tylosis palmoplantaris comprises two forms: epidermolytic and non-epidermolytic. Patients with the epidermolytic variant have up to 40% higher chance of developing squamous cell carcinoma of the esophagus. The association of tylosis palmoplantaris with esophageal cancer is called Howel-Evans syndrome.
- Published
- 2009
- Full Text
- View/download PDF
28. Mutation L437P in the 2B domain of keratin 1 causes diffuse palmoplantar keratoderma in a Chinese pedigree.
- Author
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Liu XP, Ling J, Xiong H, Shi XL, Sun X, Pan Q, Hu ZM, Wu LQ, Liang DS, Long ZG, Dai HP, Xia JH, and Xia K
- Subjects
- China, Female, Genetic Predisposition to Disease ethnology, Genetic Predisposition to Disease genetics, Genotype, Humans, Intermediate Filaments pathology, Keratoderma, Palmoplantar, Diffuse pathology, Male, Phenotype, Keratin-1 genetics, Keratoderma, Palmoplantar, Diffuse ethnology, Keratoderma, Palmoplantar, Diffuse genetics, Mutation, Missense genetics, Pedigree
- Abstract
Diffuse palmoplantar keratoderma (DPPK) is an autosomal dominant genodermatosis characterized by uniform hyperkeratosis of the palm and sole epidermis. This disorder can be caused by mutations in the genes keratin 1, keratin 9, keratin 16, desmoglein 1 and plakoglobin. Here we present a DPPK Chinese pedigree and identify the aetiology as a novel missense mutation, L437P, located in a highly conserved helix motif in domain 2B of KRT1. Functional analysis shows that overexpression of the L437P mutant in cultured cells leads to abnormal intermediate filament networks and filament aggregation. This gain-of-function mutation highlights the role of domain 2B in mediating filament assembly.
- Published
- 2009
- Full Text
- View/download PDF
29. Genetics of gastroesophageal cancer: paradigms, paradoxes, and prognostic utility.
- Author
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Robertson EV and Jankowski JA
- Subjects
- Barrett Esophagus genetics, Esophageal Neoplasms complications, Esophageal Neoplasms pathology, Humans, Keratoderma, Palmoplantar, Diffuse complications, Keratoderma, Palmoplantar, Diffuse genetics, Pedigree, Prognosis, Esophageal Neoplasms genetics
- Abstract
Hereditary diffuse gastric cancer and tylosis are autosomal dominant cancer susceptibility syndromes. Accumulating evidence also suggests a genetic contribution to Barrett's esophagus and adenocarcinoma, traditionally considered acquired disorders. In this article we review the current knowledge on the genetic mechanisms underlying hereditary diffuse gastric cancer, tylosis, and Barrett's esophagus. Hereditary diffuse gastric cancer is a paradigm for hereditary cancer susceptibility syndromes with E-cadherin implicated as the dominant oncogene in up to one-third of cases. Tylosis in contrast remains the paradox as whilst the putative abnormality has been localized to the long arm of chromosome 17, sequencing of this region has failed to reveal a disease causing mutation. In the case of Barrett's esophagus and adenocarcinoma, although a validated specific disease-associated gene is yet to be identified, the increasing body of evidence of a possible genetic link is paving the way for subsequent prognostic studies such as AspECT (Aspirin Esomeprazole Chemoprevention Trial). For the clinician these advances in understanding are already having implications for practice in terms of improved screening and the stratification of management strategies. As the mechanisms continue to be defined, there is the real possibility that these mechanisms could be exploited or subverted in the design of new therapies. In the meantime, however, clinicians should undertake rigorous biopsy programs to ensure early invasive lesions are detected.
- Published
- 2008
- Full Text
- View/download PDF
30. [Pathological features and gene mutation analysis in two pedigrees of diffuse palmoplantar keratoderma].
- Author
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Yin XZ, Zhang BR, Ding MP, Zhang H, Xia K, and Hu ZM
- Subjects
- Adolescent, Adult, DNA Mutational Analysis, Epidermis pathology, Female, Humans, Immunohistochemistry, Keratoderma, Palmoplantar pathology, Keratoderma, Palmoplantar, Diffuse pathology, Keratoderma, Palmoplantar, Epidermolytic genetics, Keratoderma, Palmoplantar, Epidermolytic pathology, Male, Middle Aged, Mutation, Pedigree, Exons genetics, Keratin-9 genetics, Keratoderma, Palmoplantar genetics, Keratoderma, Palmoplantar, Diffuse genetics, Mutation, Missense
- Abstract
We report the clinical and pathological features of two pedigrees of palmoplantar keratoderma (PPK), the expression of keratin 9 (K9) in palm tissue and the mutation of the keratin 9 gene (KRT9). Histopathology and immunohistochemical assessment was performed to analyze the epidermis in the palm of the probands. Genomic DNA of 46 family individuals was used for amplification of exon 1 of KRT9. The mutations were determined by direct sequencing. Epidermal abnormalities in the palm of the two probands were characterized by vacuolar changes of suprabasal keratinocytes accompanied by thickening of the living epidermis and stratum corneum. K9 was also expressed in particular epithelial tissues. Direct sequencing of polymerase chain reaction products revealed heterozygous missense mutations in exon 1 of KRT9 (N160S and L167S) in the two families, respectively. N160S and L167S of KRT9 are disease-causing mutations in these two Chinese pedigrees with epidermolytic palmoplanter keratoderma (EPPK).
- Published
- 2007
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- View/download PDF
31. [Autosomal dominant punctate palmoplantar keratoderma (Buschke-Fischer-Brauer disease)].
- Author
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Kluger N, Augias D, and Guillot B
- Subjects
- Aged, Humans, Keratoderma, Palmoplantar, Diffuse genetics, Male, Keratoderma, Palmoplantar, Diffuse pathology
- Published
- 2007
- Full Text
- View/download PDF
32. Keratoderma hereditarium mutilans (Vohwinkel syndrome) in three siblings.
- Author
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ul Bari A
- Subjects
- Adult, Female, Humans, Male, Syndrome, Keratoderma, Palmoplantar, Diffuse diagnosis, Keratoderma, Palmoplantar, Diffuse genetics
- Abstract
Vohwinkel syndrome or keratoderma hereditaria mutilans is a rare, diffuse, honeycombed, palmar and plantar keratosis usually accompanied by pseudoainhum near the distal interphalangeal creases. The syndrome is reported in three out of five siblings (two brothers and one sister), who developed this problem in early childhood.
- Published
- 2006
33. Down-regulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression.
- Author
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McRonald FE, Liloglou T, Xinarianos G, Hill L, Rowbottom L, Langan JE, Ellis A, Shaw JM, Field JK, and Risk JM
- Subjects
- Cell Line, Tumor, Cytoglobin, Down-Regulation, Esophageal Neoplasms metabolism, Esophageal Neoplasms pathology, Female, Gene Expression Profiling, Globins metabolism, Humans, Keratoderma, Palmoplantar, Diffuse metabolism, Male, Sequence Analysis, DNA, Allelic Imbalance, Chromosomes, Human, Pair 17, Esophageal Neoplasms genetics, Globins genetics, Keratoderma, Palmoplantar, Diffuse genetics
- Abstract
Tylosis (focal non-epidermolytic palmoplantar keratoderma) is an autosomal dominant skin disorder that is associated with the early onset of squamous cell oesophageal cancer (SCOC) in three families. Our previous linkage and haplotype analyses have mapped the tylosis with oesophageal cancer (TOC) locus to a 42.5 kb region on chromosome 17q25 that has also been implicated in the aetiology of sporadically occurring SCOC from a number of different geographical populations. Oesophageal cancer is one of the 10 leading causes of cancer mortality worldwide. No inherited disease-causing mutations have been identified in the genes located in the 42.5 kb minimal region. We now show that cytoglobin gene expression in oesophageal biopsies from tylotic patients is dramatically reduced by approximately 70% compared with normal oesophagus. Furthermore, both alleles are equally repressed. Given the autosomal dominant nature of the disease, these results exclude haploinsufficiency as a mechanism of the disease and instead suggest a novel trans-allele interaction. We also show that the promoter is hypermethylated in sporadic oesophageal cancer samples: this may constitute the 'second hit' of a gene previously implicated in this disease by allelic imbalance studies.
- Published
- 2006
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- View/download PDF
34. Hereditary diffuse palmoplantar keratodermas in Slovenia: epidemiologic foci in remote rural areas.
- Author
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Miljković J, Kansky A, and Vidmar G
- Subjects
- Genetic Predisposition to Disease epidemiology, Genetic Predisposition to Disease genetics, Humans, Keratoderma, Palmoplantar, Diffuse genetics, Population Surveillance, Prevalence, Risk Factors, Slovenia epidemiology, Keratoderma, Palmoplantar, Diffuse congenital, Keratoderma, Palmoplantar, Diffuse epidemiology, Risk Assessment methods, Rural Population statistics & numerical data
- Abstract
Background: Previous studies carried out in Slovenia revealed a high frequency of cases of hereditary diffuse palmoplantar keratodermas (DPPK). The relatively small total population of about two million in a small territory and an efficient public health service were favorable preconditions for such a study., Methods: Existing hospital and outpatient department records served as starting points. Patients were invited to come for a follow-up examination, and visiting the patients at their homes enabled us to gather further data. Thus efforts were made to include all patients with hereditary DPPK in Slovenia., Results: Altogether 170 DPPK patients were detected, giving a prevalence of 8.3 per 100,000 inhabitants. The patients originated from remote, mostly mountainous districts, where the local DPPK prevalence highly significantly exceeded the average Slovene prevalence. The segregation ratio showed an autosomal dominant mode of inheritance. The percentage of persons affected was 34.4% (95% confidence interval 29.8-39.4), lower than expected for autosomal dominant inheritance (the difference is highly significant, P < 0.00001; exact binomial test)., Conclusion: One autosomal dominant gene alone does not fully explain the transmission of the disorder to siblings. Evidence is produced that additional factors are necessary for the transmission of this genetic condition. The degree of consanguinity and the physical pressure on palms and soles seem to play an important part. It is reasonable to expect that molecular-biology studies linked to the epidemiological data could contribute to the solution of the problem.
- Published
- 2006
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- View/download PDF
35. A novel mutation and large size polymorphism affecting the V2 domain of keratin 1 in an African-American family with severe, diffuse palmoplantar keratoderma of the ichthyosis hystrix Curth-Macklin type.
- Author
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Richardson ES, Lee JB, Hyde PH, and Richard G
- Subjects
- Adolescent, Adult, Amino Acid Sequence, Base Sequence, Female, Glycine genetics, Humans, Keratin-1, Keratoderma, Palmoplantar, Diffuse pathology, Male, Molecular Sequence Data, Mutation, Protein Structure, Tertiary genetics, Black or African American genetics, Keratins genetics, Keratoderma, Palmoplantar, Diffuse genetics, Polymorphism, Genetic, Sequence Deletion
- Abstract
Keratin gene mutations affecting nonhelical head and tail domains are not usually associated with prominent skin blistering and keratin filament clumping. Instead, they have been associated with several distinct clinical phenotypes, such as epidermolysis bullosa simplex with mottled pigmentation (mutation P25L in the V1 domain of keratin 5), epidermolysis bullosa simplex with migratory circinate erythema (frameshift mutation c1649delG in the V2 domain of keratin 5), striate palmoplantar keratoderma (PPK), and ichthyosis hystrix Curth-Macklin (different frameshift mutations in the V2 domain of keratin 1 (K1)). We have studied a family with severe, diffuse, nonepidermolytic PPK and verrucous hyperkeratotic plaques over the joints and in flexures and identified a new KRT1 gene mutation that is predicted to completely alter the K1 tail domain. In addition, a new K1 size polymorphism has been detected, which is especially prevalent among the African-American population. These results further emphasize the functional importance of the nonhelical tail domain in keratin molecules despite the obvious variability in the number of glycine loop motifs and underscore the broad phenotypic spectrum of disorders due to dominant keratin tail mutations.
- Published
- 2006
- Full Text
- View/download PDF
36. [Hotspot of the mutations of keratin 9 gene in a diffuse palmoplantar keratoderma family].
- Author
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Sun X, Yin XZ, Wu LQ, Shi XL, Hu ZM, Liu XP, Pan Q, Dai HP, Xia K, and Xia JH
- Subjects
- Base Sequence, DNA Mutational Analysis, Female, Humans, Male, Molecular Sequence Data, Pedigree, Heterozygote, Keratins genetics, Keratoderma, Palmoplantar, Diffuse genetics, Mutation
- Abstract
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.
- Published
- 2005
37. Diagnosis of epidermolytic palmoplantar keratoderma in a very early stage by gene analysis.
- Author
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Shimazu K, Tsunemi Y, Hattori N, Adachi M, Imakado S, Saeki H, Komine M, and Tamaki K
- Subjects
- Amino Acid Substitution, Female, Humans, Infant, Keratoderma, Palmoplantar, Diffuse genetics, Keratoderma, Palmoplantar, Diffuse pathology, Skin pathology, Keratins genetics, Keratoderma, Palmoplantar, Diffuse diagnosis, Point Mutation
- Published
- 2005
- Full Text
- View/download PDF
38. The common KRT9 gene mutation in a Japanese patient with epidermolytic palmoplantar keratoderma and knuckle pad-like keratoses.
- Author
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Hamada T, Ishii N, Karashima T, Kawano Y, Yasumoto S, and Hashimoto T
- Subjects
- Adolescent, Base Sequence, DNA Mutational Analysis, Follow-Up Studies, Foot Dermatoses, Hand Dermatoses, Humans, Japan, Keratoderma, Palmoplantar, Diffuse diagnosis, Keratosis genetics, Male, Molecular Sequence Data, Polymerase Chain Reaction, Risk Assessment, Severity of Illness Index, Genetic Predisposition to Disease, Keratins genetics, Keratoderma, Palmoplantar, Diffuse genetics, Mutation
- Published
- 2005
- Full Text
- View/download PDF
39. Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer locus in sporadic oesophageal squamous cell carcinomas.
- Author
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Iwaya T, Maesawa C, Kimura T, Ogasawara S, Ikeda K, Kimura Y, Noda Y, Ishida K, Sato N, Saito K, and Masuda T
- Subjects
- Alleles, Cell Line, Tumor, Codon, DNA Primers chemistry, DNA, Complementary metabolism, Exons, Genetic Linkage, Humans, Loss of Heterozygosity, Microsatellite Repeats, Models, Genetic, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Polymorphism, Single-Stranded Conformational, Protein Conformation, Protein Structure, Tertiary, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Time Factors, Carcinoma, Squamous Cell genetics, Esophageal Neoplasms genetics, Keratoderma, Palmoplantar, Diffuse genetics, Membrane Proteins genetics, Membrane Proteins physiology, Mutation, Protein Precursors genetics, Protein Precursors physiology
- Abstract
Envoplakin (EVPL) is a member of the desmosomal plaque proteins attached to desmosomal cadherin and keratin filaments. The EVPL gene has been mapped to the tylosis oesophageal cancer (TOC) locus on chromosome 17q25, where it has been demonstrated to be frequently deleted in both familial and sporadic forms of oesophageal squamous cell carcinoma (OSC). In this study, we examined EVPL gene mutations in 10 OSC cell lines and 20 sporadic OSCs using reverse transcription-polymerase chain reaction single-strand conformational analysis (RT-PCR SSCP) followed by direct sequencing. We observed one somatic mutation (GCG to ACG at codon 1104, Ala to Thr: 1/20, 5%) in the central rod domain and 5 intragenic polymorphic sites, where frequent loss of heterozygosity (LOH) (63%) was detected. No mutations were detected in the OSC cell lines. The rate of EVPL gene mutation was quite low in contrast to the frequency of LOH on the TOC locus in sporadic OSCs, and the high incidence of oesophageal cancer development in tylosis families. Our results suggest that EVPL might not be the target gene responsible for OSC, despite its strong candidacy in terms of character and localization.
- Published
- 2005
40. Palmoplantar keratodermas.
- Author
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Itin PH and Fistarol SK
- Subjects
- Biopsy, Needle, Connexins genetics, Desmosomes genetics, Female, Humans, Immunohistochemistry, Incidence, Keratins genetics, Keratoderma, Palmoplantar epidemiology, Keratoderma, Palmoplantar, Diffuse diagnosis, Keratoderma, Palmoplantar, Diffuse epidemiology, Keratoderma, Palmoplantar, Diffuse genetics, Male, Prognosis, Risk Assessment, Severity of Illness Index, Sex Distribution, Genetic Predisposition to Disease, Keratoderma, Palmoplantar diagnosis, Keratoderma, Palmoplantar genetics
- Abstract
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.
- Published
- 2005
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- View/download PDF
41. An investigation of the tylosis with oesophageal cancer (TOC) locus in Iranian patients with oesophageal squamous cell carcinoma.
- Author
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Shahabi M, Noori Daloii MR, Langan JE, Rowbottom L, Jahanzad E, Khoshbin E, Taghikhani M, Field JK, and Risk JM
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell secondary, Cytoglobin, Esophageal Neoplasms pathology, Exons genetics, Female, Globins, Humans, Iran, Keratoderma, Palmoplantar, Diffuse complications, Male, Microsatellite Repeats genetics, Middle Aged, Peroxidases genetics, Polymorphism, Single Nucleotide, Allelic Imbalance, Carcinoma, Squamous Cell genetics, Chromosomes, Human, Pair 17 genetics, Esophageal Neoplasms genetics, Keratoderma, Palmoplantar, Diffuse genetics
- Abstract
Oesophageal cancer is one of the ten leading causes of cancer mortality worldwide. Earlier loss of heterozygosity (or allelic imbalance) studies have implicated regions on chromosomes 3p, 5q, 9p, 13q, 17p, 17q, and 18q in the development of sporadic oesophageal cancer and recent data have linked the familial tylosis with oesophageal cancer (TOC) gene-containing region on chromosome 17q25 with this cancer. We have studied allelic imbalance (AI) at microsatellite markers both closely linked to and distant from the TOC gene locus in 60 sporadic squamous cell oesophageal cancers from Iran and have investigated the most likely candidate gene by mutation analysis in these tumours. Forty-four out of these 60 samples (73%) show allelic imbalance at one or more loci within or adjacent to the TOC minimal region, while the highest incidence of AI was observed at the D17S2244 and D17S2246 loci (almost 70% AI in informative cases), correlating with the TOC minimal region. Analysis of the coding regions of a candidate gene in these tumours failed to show an equivalently high incidence of mutation, although two mutations and one polymorphism were observed. These data support and extend previous observations that the TOC region of chromosome 17q25 may be involved in the aetiology of the sporadic form of oesophageal cancer from a number of different geographical populations and suggest that the causative gene may be epigenetically silenced rather than mutated.
- Published
- 2004
- Full Text
- View/download PDF
42. Novel microsatellite markers and single nucleotide polymorphisms refine the tylosis with oesophageal cancer (TOC) minimal region on 17q25 to 42.5 kb: sequencing does not identify the causative gene.
- Author
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Langan JE, Cole CG, Huckle EJ, Byrne S, McRonald FE, Rowbottom L, Ellis A, Shaw JM, Leigh IM, Kelsell DP, Dunham I, Field JK, and Risk JM
- Subjects
- Base Sequence, DNA Primers, Electrophoresis, Polyacrylamide Gel, Esophageal Neoplasms complications, Haplotypes genetics, Humans, Keratoderma, Palmoplantar, Diffuse complications, Microsatellite Repeats genetics, Polymorphism, Single Nucleotide genetics, Sequence Analysis, DNA, United Kingdom, United States, Chromosome Mapping, Chromosomes, Human, Pair 17 genetics, Esophageal Neoplasms genetics, Keratoderma, Palmoplantar, Diffuse genetics, Pedigree
- Abstract
Tylosis (focal non-epidermolytic palmoplantar keratoderma) is associated with the early onset of squamous cell oesophageal cancer in three families. Linkage and haplotype analyses have previously mapped the tylosis with oesophageal cancer ( TOC) locus to a 500-kb region on chromosome 17q25 that has also been implicated in sporadically occurring squamous cell oesophageal cancer. In the current study, 17 additional putative microsatellite markers were identified within this 500-kb region by using sequence data and seven of these were shown to be polymorphic in the UK and US families. In addition, our complete sequence analysis of the non-repetitive parts of the TOC minimal region identified 53 novel and six known single nucleotide polymorphisms (SNPs) in one or both of these families. Further fine mapping of the TOC disease locus by haplotype analysis of the seven polymorphic markers and 21 of the 59 SNPs allowed the reduction of the minimal region to 42.5 kb. One known and two putative genes are located within this region but none of these genes shows tylosis-specific mutations within their protein-coding regions. Alternative mechanisms of disease gene action must therefore be considered.
- Published
- 2004
- Full Text
- View/download PDF
43. An unusual case of palmoplantar keratoderma.
- Author
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Devos SA and Delescluse J
- Subjects
- Acitretin therapeutic use, Female, Humans, Hyperhidrosis complications, Keratolytic Agents therapeutic use, Middle Aged, Keratoderma, Palmoplantar, Diffuse drug therapy, Keratoderma, Palmoplantar, Diffuse genetics
- Abstract
A 55-year-old woman with palmoplantar keratoderma presented an associated hyperhidrosis with distinct odour and maceration. She had had the lesions for about 20 years and this seemed to be an isolated case in her family. This case appeared very unusual because there were no signs of acanthokeratolysis in the biopsies. Two months of treatment with acitretin (Neotigason; 25 mg daily), produced a spectacular result: clearance of all the lesions on both hands and a strong diminution of the lesions on the soles. The Unna-Thost variant of palmoplantar keratoderma usually appears in the first few months of life, and it rarely appears in the third decade. The condition is inherited as an autosomal dominant with high penetrance and expressivity. Our subject appeared to be an exception to these two facts.
- Published
- 2003
- Full Text
- View/download PDF
44. A keratin 9 Gene mutation (Asn160Ser) in a Japanese patient with epidermolytic palmoplantar keratoderma.
- Author
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Tsunemi Y, Hattori N, Saeki H, Adachi M, Komine M, Nakagawa H, and Tamaki K
- Subjects
- Biopsy, Needle, Child, Preschool, DNA Mutational Analysis, Female, Humans, Immunohistochemistry, Japan, Keratoderma, Palmoplantar, Diffuse ethnology, Keratoderma, Palmoplantar, Diffuse pathology, Point Mutation, Asian People genetics, Genetic Predisposition to Disease, Keratins genetics, Keratoderma, Palmoplantar, Diffuse genetics, Mutation, Polymerase Chain Reaction
- Abstract
We described a 5-year-old Japanese girl with epidermolytic palmoplantar keratoderma and examined her for a keratin 9 gene mutation. Physical examination disclosed diffuse yellowish hyperkeratosis with an erythematous border limited strictly to the palms and soles. Histological examination revealed hyperkeratosis with vacuolar degeneration in the spinous and granular layers of the epidermis. Sequence analysis demonstrated an A to G transition at the middle position of codon 160 in the 1A domain of the keratin 9 gene. The amino acid at codon 160 was deduced to have changed from asparagine (Asn) to serine (Ser). This is the first case with an Asn160Ser mutation in a Japanese. The substitution of Ser for Asn at codon 160 of the keratin 9 gene is assumed to be fatal for keratin filament assembly regardless of race or ethnicity.
- Published
- 2002
- Full Text
- View/download PDF
45. Carcinoma of stomach in a patient with familial tylosis.
- Author
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Wagle PK, Shetty TS, Darbari A, Tapia AA, Katrak MP, and Joshi RM
- Subjects
- Adenocarcinoma genetics, Humans, Keratoderma, Palmoplantar, Diffuse genetics, Male, Middle Aged, Stomach Neoplasms genetics, Adenocarcinoma complications, Keratoderma, Palmoplantar, Diffuse complications, Stomach Neoplasms complications
- Abstract
The association of tylosis with esophageal cancer has been extensively reported but association with gastric cancer is rare. We report a 55-year-old man with familial tylosis and carcinoma of the stomach for which radical gastrectomy was done. Repeat endoscopy 3 years later is normal.
- Published
- 2002
46. Characterization of a 500 kb region on 17q25 and the exclusion of candidate genes as the familial Tylosis Oesophageal Cancer (TOC) locus.
- Author
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Risk JM, Evans KE, Jones J, Langan JE, Rowbottom L, McRonald FE, Mills HS, Ellis A, Shaw JM, Leigh IM, Kelsell DP, and Field JK
- Subjects
- Carcinoma, Squamous Cell etiology, Chromosome Mapping, Esophageal Neoplasms etiology, Genes, Tumor Suppressor, Humans, Keratoderma, Palmoplantar, Diffuse etiology, Carcinoma, Squamous Cell genetics, Chromosomes, Human, Pair 17, Esophageal Neoplasms genetics, Keratoderma, Palmoplantar, Diffuse genetics
- Abstract
The locus for a syndrome of focal palmoplantar keratoderma (Tylosis) associated with squamous cell oesophageal cancer (TOC) has been mapped to chromosome 17q25, a region frequently deleted in sporadic squamous cell oesophageal tumours. Further haplotype analysis described here, based on revised maps of marker order, has reduced the TOC minimal region to a genetic interval of 2 cM limited by the microsatellite markers D17S785 and D17S751. Partial sequence data and complete physical maps estimate the actual size of this region to be only 0.5 Mb. This analysis allowed the exclusion of proposed candidate tumour suppressor genes including MLL septin-like fusion (MSF), survivin, and deleted in multiple human cancer (DMC1). Computer analysis of sequence data from the minimal region identified 13 candidate genes and the presence of 50-70 other 'gene fragments' as ESTs and/or predicted exons and genes. Ten of the characterized genes were assayed for mutations but no disease-specific alterations were identified in the coding and promoter sequences. This region of chromosome 17q25 is, therefore, relatively gene-rich, containing 13 known and possibly as many as 50 predicted genes. Further mutation analysis of these predicted genes, and others possibly residing in the region, is required in order to identify the elusive TOC locus.
- Published
- 2002
- Full Text
- View/download PDF
47. Connexin disorders of the skin.
- Author
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Richard G
- Subjects
- Animals, Connexins physiology, Ectodermal Dysplasia pathology, Gap Junctions physiology, Humans, Keratoderma, Palmoplantar pathology, Keratoderma, Palmoplantar, Diffuse genetics, Keratoderma, Palmoplantar, Diffuse pathology, Mutation, Phenotype, Connexins genetics, Ectodermal Dysplasia genetics, Keratoderma, Palmoplantar genetics
- Published
- 2001
48. Transgrediens et progrediens palmoplantar keratoderma (Greither's disease) with particular histopathologic findings.
- Author
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Grilli R, Aguilar A, Escalonilla P, Soriano L, Fariña C, Martín L, and Requena L
- Subjects
- Biopsy, Needle, Diagnosis, Differential, Female, Humans, Keratoderma, Palmoplantar genetics, Keratoderma, Palmoplantar pathology, Keratoderma, Palmoplantar, Diffuse genetics, Middle Aged, Pedigree, Prognosis, Keratoderma, Palmoplantar, Diffuse pathology
- Abstract
We describe a patient with transgrediens et progrediens palmoplantar keratoderma (Greither's disease). Ten of the 25 members of this patient's family in six consecutive generations were affected by the disorder. The pedigree was consistent with an autosomal dominant inheritance pattern, with variable penetrance. The proband's physical examination showed typical signs of Greither's disease. The most striking findings were seen in histopathologic study and consisted of round, focal areas of orthohyperkeratosis located on delled areas of the epidermis. These histopathologic features were present in both the lesions of the palms and dorsum of the hands. We review the clinical manifestations and histopathologic findings of this particular variant of palmoplantar keratoderma and the differential diagnosis.
- Published
- 2000
49. Fine genetic mapping of diffuse non-epidermolytic palmoplantar keratoderma to chromosome 12q11-q13: exclusion of the mapped type II keratins.
- Author
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Kelsell DP, Stevens HP, Purkis PE, Talas U, Rustin MH, and Leigh IM
- Subjects
- Chromosome Mapping, Female, Genetic Linkage, Haplotypes, Humans, Keratoderma, Palmoplantar, Diffuse pathology, Male, Microsatellite Repeats, Multigene Family, Pedigree, Chromosomes, Human, Pair 12 genetics, Keratins genetics, Keratoderma, Palmoplantar, Diffuse genetics
- Abstract
Diffuse non-epidermolytic palmoplantar keratoderma (NEPPK) belongs to the heterogeneous group of skin diseases characterized by thickening of the stratum corneum of the palms and soles (1). This autosomal dominant PPK is characterized by a diffuse pattern of palmar and plantar hyperkeratosis giving the affected areas a thickened yellowish appearance with a marked erythematous edge. Linkage of diffuse NEPPK to chromosome 12q11-q13 has been demonstrated in two independent reports (2, 3). In this study, we describe detailed haplotyping with microsatellite markers mapping to this chromosomal region in three diffuse NEPPK pedigrees from the south of England. Fine mapping of a previously identified recombination event and the identification of a common disease haplotype segregating in the three pedigrees places the diffuse NEPPK locus proximal to the type II keratin gene cluster.
- Published
- 1999
- Full Text
- View/download PDF
50. Envoplakin, a possible candidate gene for focal NEPPK/esophageal cancer (TOC): the integration of genetic and physical maps of the TOC region on 17q25.
- Author
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Risk JM, Ruhrberg C, Hennies H, Mills HS, Di Colandrea T, Evans KE, Ellis A, Watt FM, Bishop DT, Spurr NK, Stevens HP, Leigh IM, Reis A, Kelsell DP, and Field JK
- Subjects
- Base Sequence, Chromosomes, Human, Pair 17 genetics, DNA chemistry, DNA genetics, Exons, Family Health, Genes genetics, Haplotypes, Humans, Introns, Molecular Sequence Data, Pedigree, Physical Chromosome Mapping, Sequence Analysis, DNA, Esophageal Neoplasms genetics, Keratoderma, Palmoplantar, Diffuse genetics, Membrane Proteins genetics, Protein Precursors genetics
- Abstract
Focal nonepidermolytic palmoplantar keratoderma (NEPPK), or tylosis, is an autosomal, dominantly inherited disorder of the skin that manifests as focal thickening of the palmar and plantar surfaces. In three families studied, the skin disorder cosegregates with esophageal cancer and oral lesions. New haplotype analysis, presented here, places the tylosis esophageal cancer (TOC) locus between D17S1839 and D17S785. Envoplakin (EVPL) is a protein component of desmosomes and the cornified envelope that is expressed in epidermal and esophageal keratinocytes and has been localized to the TOC region. Mutation analysis of EVPL in the three affected families failed to show tylosis-specific mutations, and haplotype analysis of three intragenic sequence polymorphisms of the EVPL gene placed it proximal to D17S1839. Confirmation of the exclusion of EVPL as the TOC gene by location was obtained by integration of the genetic and physical mapping data using radiation hybrid, YAC, BAC, and PAC clones. This new physical map will allow further identification of candidate genes underlying NEPPK associated with esophageal cancer, which may also be implicated in the development of sporadic squamous cell esophageal carcinoma and Barrett's adenocarcinoma., (Copyright 1999 Academic Press.)
- Published
- 1999
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