Olmsted syndrome

Mevorah, B.; Goldberg, Ilan; Sprecher, Eli; Bergman, Reuven; Metzker, Aryeh; Luria, R.; Gat, Andrea; Brenner, Sarah

doi:10.1016/j.jaad.2005.03.036

Cited by 46 publications

(16 citation statements)

References 34 publications

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“…17 No mutations have been detected in 3 other genes namely KRT1 (Keratin 1), GJB2 (Gap junction protein b 2) and SLURP1 (Secreted Ly-6/uPAR-related protein 1); which are otherwise involved in other skin-related problems. 4,17 A missense mutation in membranebound transcription factor protease site 2 (MBTPS2) is involved in OS, though the molecular mechanisms remain uncharacterized. 28 Though involvement of other candidate genes in OS cannot be ruled out at this stage; involvement of TRPV3 is highly significant.…”

Section: Discussionmentioning

confidence: 99%

“…2 These patients develop clinical symptoms of bilateral mutilating palmoplantar keratoderma and periorifacial keratotic plaques. [3][4][5][6][7][8][9] Severe itching at the affected regions, impaired hair growth, hearing loss, and loss of terminal portion of the limbs, auto-amputation of digits, loss-of-bones and/or osteonecrosis are other specific features of OS. [9][10][11] There is no satisfactory treatment for this disease as different agents such as salicylic acid, urea, boric acid, shale oil, retinoic acids, corticosteroids, anti-microbial drugs, antihistamines, vitamin-E, vitamin-A and other emollients failed to improve the pathological conditions.…”

Section: Introductionmentioning

confidence: 99%

“…[4][5]8,11,17,18 The exact mode of inheritance of OS is not well established. Sporadic occurrence, autosomaldominant, X-linked dominant and X-linked recessive modes of inheritance had been proposed.…”

Section: Introductionmentioning

confidence: 99%

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TRPV3 mutants causing Olmsted Syndrome induce impaired cell adhesion and nonfunctional lysosomes

Yadav

Goswami

2017

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TRPV3 is a non-selective cationic channel and is important for several physiological functions. It can be activated by physiological temperature and selective endogenous and exogenous compounds. TRPV3 is one of the key ion channel involved in Ca 2C -signaling in keratinocyte and thus involved in skin-related functions. Recently, naturally occurring mutations in TRPV3, namely G573A, G573S, G573C and W692G have been detected which are linked with the development of pathophysiological conditions such as Olmsted Syndrome (OS) and other skin disorders. Our qualitative and quantitative data suggests that these naturally occurring TRPV3 mutants are mainly restricted in the ER. Expression of OS-mutants cause impaired vesicular trafficking resulting reduced surface localization of these mutants and other membrane proteins too. OS-mutants also cause reduced cell adhesion, altered distribution and less number of lysosomes. Our data confirms that TRPV3 is a lysosomal protein suggesting that Olmsted Syndrome is a lysosomal disorder. These findings may have a broad implication in the context of keratinocyte functions, skin-degeneration and in skin-cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TRPV3 mutants causing Olmsted Syndrome induce impaired cell adhesion and nonfunctional lysosomes

Yadav

Goswami

2017

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“…The diagnosis of these disorders relies upon clinical features (e.g. pseudoainhum in MDM [10], dental problems in Papillon-Lefèvre syndrome [10], hearing loss in Olmsted syndrome [11]) as well as histopathological findings (e.g. epidermolytic changes in EPPK, retained nuclei in the stratum corneum in loricrin keratoderma, keratinocytes disadhesion in keratosis palmoplantaris striata and binuclear granular cells in ichthyosis hystrix) [12,13,14,15].…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of High-Resolution Multifrequency Ultrasound of the Plantar Skin in Patients with Various Types of Hereditary Palmoplantar Keratoderma

et al. 2013

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Background: High-variable-frequency ultrasound is used as an imaging tool for various cutaneous disorders. We utilized this tool in pachyonychia congenita (PC) patients, who typically present with plantar hyperkeratosis and often severely debilitating pain, compared to patients with epidermolytic palmoplantar keratoderma (EPPK) and mal de Meleda (MDM). Objective: To ascertain the feasibility of ultrasound technology for the diagnosis of PC. Methods: The study included a total of 16 patients, 7 with PC, 5 with EPPK and 4 with MDM, who underwent ultrasound examination of the plantar skin with high-resolution multifrequency ultrasound equipment. Results: Ultrasound scans performed over the proximal and distal plantar foot calluses in PC patients demonstrated hyperechoic dots and lines within the epidermis compatible with hyperkeratosis, engorged varicose veins in the dermis and an anechoic layer interposed between the epidermis and the dermis, corresponding to blister fluid below the calluses. In contrast to PC patients, patients with MDM and EPPK demonstrated no blisters. Conclusion: PC patients, as opposed to a group of patients with MDM and EPPK, displayed subepidermal blistering beneath their calluses. This finding may help in the diagnosis of PC and in partially explaining plantar pain as part of PC symptomatology.

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“…Expression of TRPV3 in keratinocytes and in vitro studies suggest that elevated keratinocyte apoptosis could drive disease [2], however it should be noted that TRPV3 is also expressed by Langerhans dendritic cells in the skin [6], and thus an immunological origin for disease cannot be excluded. A review of published cases noted the common concordance of recurrent bacterial and candida infections in keratotic areas [7], supporting a link between dermal and immunological defects which has not been further explored.…”

Section: Introductionmentioning

confidence: 99%

Olmsted syndrome: exploration of the immunological phenotype

Danso-Abeam

Zhang

Dooley

et al. 2013

Orphanet J Rare Dis

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BackgroundOlmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome.MethodsGenetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome.ResultsThe patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood.ConclusionsThese results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients.

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Olmsted syndrome

Cited by 46 publications

References 34 publications

TRPV3 mutants causing Olmsted Syndrome induce impaired cell adhesion and nonfunctional lysosomes

TRPV3 mutants causing Olmsted Syndrome induce impaired cell adhesion and nonfunctional lysosomes

Comparative Study of High-Resolution Multifrequency Ultrasound of the Plantar Skin in Patients with Various Types of Hereditary Palmoplantar Keratoderma

Olmsted syndrome: exploration of the immunological phenotype

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