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1.
Commun Biol ; 2: 375, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31633066

RESUMO

Synaptosomal-associated protein 29 (SNAP29) encodes a member of the SNARE family of proteins implicated in numerous intracellular protein trafficking pathways. SNAP29 maps to the 22q11.2 region and is deleted in 90% of patients with 22q11.2 deletion syndrome (22q11.2DS). Moreover, bi-allelic SNAP29 mutations in patients are responsible for CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma) syndrome. A mouse model that recapitulates abnormalities found in these syndromes is essential for uncovering the cellular basis of these disorders. In this study, we report that mice with a loss of function mutation of Snap29 on a mixed CD1;FvB genetic background recapitulate skin abnormalities associated with CEDNIK, and also phenocopy neurological and ophthalmological abnormalities found in CEDNIK and a subset of 22q11.2DS patients. Our work also reveals an unanticipated requirement for Snap29 in male fertility and supports contribution of hemizygosity for SNAP29 to the phenotypic spectrum of abnormalities found in 22q11.2DS patients.


Assuntos
Síndrome de DiGeorge/genética , Ceratodermia Palmar e Plantar/genética , Síndromes Neurocutâneas/genética , Proteínas Qb-SNARE/deficiência , Proteínas Qb-SNARE/genética , Proteínas Qc-SNARE/deficiência , Proteínas Qc-SNARE/genética , Animais , Síndrome de DiGeorge/patologia , Síndrome de DiGeorge/fisiopatologia , Modelos Animais de Doenças , Anormalidades do Olho/genética , Anormalidades do Olho/patologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Hemizigoto , Humanos , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Ceratodermia Palmar e Plantar/patologia , Ceratodermia Palmar e Plantar/fisiopatologia , Mutação com Perda de Função , Masculino , Camundongos , Camundongos Knockout , Camundongos Mutantes , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/patologia , Síndromes Neurocutâneas/patologia , Síndromes Neurocutâneas/fisiopatologia , Fenótipo , Gravidez
2.
Ann Dermatol Venereol ; 146(11): 730-736, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31582262

RESUMO

INTRODUCTION: Development of acral malignant melanoma in Mal de Meleda is highly unusual. As far as we could ascertain, to date, only 10 previous cases have been published. Herein, we report a new case. OBSERVATION: A 64-year-old Algerian man was followed for familial Mal de Meleda. The diagnosis was based on clinical presentation as he had a non-syndromic hereditary foul-smelling and yellowish palmoplantar keratoderma transgrediens. After the failure of acitretin, which had not prevented retractile and mutilating progression of the palmoplantar keratoderma, he had undergone surgery with graft excision of both palms. At the age of 59 years, he presented a tumor on the dorsal aspect of the 1st phalanx of the 3rd finger of the right hand in a non-grafted area. The diagnosis of acral melanoma was confirmed histologically. The radiological findings showed a specific homolateral axillary adenopathy. He underwent digital amputation of the 3rd finger, with lymph node dissection and chemotherapy involving dacarbazine. Follow-up at 5 years showed complete remission of the melanoma. DISCUSSION: Mal de Meleda is a hereditary palmoplantar keratoderma due to mutation of the SLURP1 gene. Clinical diagnosis is based on the typical phenotype in adulthood. The occurrence of acral melanoma, which is a rare form of melanoma (1 to 7%), especially in the fingers, together with an unusual palmoplantar keratoderma in a subject of type IV phototype does not appear to be a chance event. This association seems to be the outcome of immune dysregulation rather than of chronic inflammation.


Assuntos
Dedos/patologia , Ceratodermia Palmar e Plantar/patologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Humanos , Masculino , Pessoa de Meia-Idade
3.
Biomedica ; 39(2): 247-251, 2019 06 15.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31529812

RESUMO

Aquagenic keratoderma is a benign entity that is characterized by producing whitish or translucent papules a few seconds after contact with water. We present the case of a 16-year-old patient with multiple asymptomatic confluent papules that appeared on both hand palms after contact with water and which disappeared after drying. The histopathological findings in a skin biopsy after water exposure showed changes in the superficial layers of the stratum corneum and dilatation of sweat gland ducts. This entity of unknown etiology has been related to neuronal and eccrine gland dysfunction. Recently it has been associated with alterations of aquaporins. The "hand-in-the-bucket" sign is a simple useful clinical tool for diagnosis, as histopathological findings may be nonspecific. Topical treatments include barrier mechanisms and botulinum toxin.


Assuntos
Dermatoses da Mão/etiologia , Ceratodermia Palmar e Plantar/etiologia , Água/efeitos adversos , Adolescente , Biópsia , Diagnóstico Diferencial , Feminino , Dermatoses da Mão/patologia , Humanos , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/patologia
5.
Mycopathologia ; 184(5): 597-605, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31376042

RESUMO

Foot hyperkeratosis is common. They often coincide with fungal infections, are difficult to cure and relapse rates are high. In this case study, longstanding and intractable plantar hyperkeratotic lesions were investigated for potential causative agents by histological examinations, by using human cell culture medium to grow the infected skin tissue, by sequencing ribosomal DNA and whole genome. Aspergillus sydowii was identified as the pathogen in the hyperkeratotic lesions. A peculiars intracellular infection of the fungus appeared to merge with anucleated epithelial cells of the skin, in which not fungal cells but basophilic nucleus-like bodies and abundant fungal proteins were seen in the cells. The composite fungal-human zombie-like cells were found to grow in the culture and in hyperkeratotic lesions, and some were readily transformed to natural fungus. Such zombie cells might play roles in the pathogenesis and recurrences of plantar hyperkeratotic lesions, resistance to antifungal drugs and relapses of the fungal infections.


Assuntos
Aspergillus/isolamento & purificação , Queratinócitos/microbiologia , Queratinócitos/patologia , Ceratodermia Palmar e Plantar/microbiologia , Ceratodermia Palmar e Plantar/patologia , Aspergillus/classificação , Aspergillus/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Sequenciamento Completo do Genoma
6.
Dev Cell ; 50(4): 436-446.e5, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31353312

RESUMO

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.


Assuntos
Complexo 2 de Proteínas Adaptadoras/genética , Proteínas Adaptadoras de Transporte Vesicular/genética , Endocitose/genética , Sequência de Aminoácidos/genética , Membrana Celular/genética , Clatrina/genética , Humanos , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/patologia , Ligação Proteica/genética , Transporte Proteico/genética , Proteólise
7.
Clin Dermatol ; 37(3): 175-181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178100

RESUMO

Mal de Meleda is an hereditary palmoplantar keratoderma named for the Mljet Island in Croatia. The lives of those affected by this disease represent a complex situation that encompasses members of a vulnerable group. They require enlightenment and should be approached with awareness, taking into account their overall psychophysical status and the environment of each patient. Those afflicted with Mal de Meleda not only have to deal with a difficult life due to their affliction, but they also must cope with the hardships of socialization while trying to realize a normal life within their island community. This is compounded by the frequent interviews and examinations of researchers interested in the various aspects of their illness. The subject of this contribution is not about the nature of this disease, rather about the traces it has left on the (sub)consciousness of the population. It is also concerned with exploring ways of how to access patients and understanding the depth of their vulnerability. We present some thoughts tied to the interpersonal experiences of researchers and patients afflicted with Mal de Meleda.


Assuntos
Ceratodermia Palmar e Plantar , Estereotipagem , Conscientização , Croácia , Ética , História do Século XVIII , História do Século XIX , História do Século XX , História Medieval , Humanos , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/história , Ceratodermia Palmar e Plantar/patologia , Ceratodermia Palmar e Plantar/psicologia , Hanseníase , Qualidade de Vida , Distância Social , Isolamento Social , Rede Social , Percepção Social , Populações Vulneráveis
9.
Hautarzt ; 70(7): 497-505, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31087125

RESUMO

Approximately 9000 different phenotypes are known in medicine. The definition phenotype includes both manifest diseases as well as features without any disease value and the pure genetic disposition to develop a disease (e.g. tumors or complex diseases); however, most phenotypes are rare monogenic hereditary diseases. Approximately 6400 of these phenotypes have so far been elucidated by molecular genetics and are caused by mutations in 4064 different genes. Of all genetic diseases, an estimated one third are associated with skin symptoms. Genodermatoses are the phenotypes predominantly related to the skin, of which approximately 600 are familiar to dermatologists. The syndromes with scaling and keratosis include cornification disorders where the symptoms are not limited to the skin. They are associated with skin symptoms such as ichthyosis, erythroderma and palmoplantar keratoderma but show additional symptoms from other organ groups. The typical combination of symptoms may be unique to a syndrome and therefore seminal for the diagnosis.


Assuntos
Neoplasias Ósseas , Condromatose , Ictiose , Ceratodermia Palmar e Plantar , Ceratose , Mutação/genética , Síndromes Neoplásicas Hereditárias , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Condromatose/genética , Condromatose/patologia , Humanos , Ictiose/genética , Ictiose/patologia , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/patologia , Ceratose/genética , Ceratose/patologia , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia , Pele , Síndrome
10.
Clin Exp Dermatol ; 44(6): 606-612, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31074523

RESUMO

Pachyonychia congenita (PC) describes a group of genodermatoses manifesting as thickened nails, palmoplantar keratoderma (PPK) and increased risk of cutaneous infections. PC tarda (PCT) describes late-onset PC, and associated genetic polymorphisms have been identified. There has been discussion that PCT may not be a distinct entity but rather misdiagnosed ectodermal dysplasia (ED) or PPK. Clarification of this is important for appropriate diagnosis, management and patient and genetic counselling. We aimed to conduct a systematic review of all reported cases of PCT in the published literature and collate evidence of genetic polymorphisms and clinical features to compare with known features of PC, ED and PPK. PubMed (1946 to 1 July 2018), Scopus (1955 to 1 July 2018) and Web of Science (1990 to 1 July 2018) databases were searched for case reports of PCT with no search restrictions on date or language. The search strategy included the terms pachyonychia congenita tarda OR pachyonychia congenita AND (late onset OR delayed OR PCT). In total, 13 reports describing 19 individual cases of PCT were identified. Of the three identified genetic polymorphisms, the earliest identified has been shown to be highly probably pathogenic, with the second likely to result in a benign amino acid change, while the third has since been shown to be nonpathogenic,. No epigenetic studies have been performed on any reported cases. Previous authors have suggested that a number of cases of PCT may be misdiagnosed ED or PPK. The findings of our review cannot refute this suggestion, and highlight the need for thorough clinical documentation of suspected cases of PCT and thorough genetic screening of kindred to identify causative genetic polymorphisms. Further high-quality datasets and reporting are needed to give further insight into the nature of PCT as a unique entity.


Assuntos
Doenças da Unha/patologia , Unhas Malformadas/patologia , Paquioníquia Congênita/patologia , Adolescente , Adulto , Criança , Erros de Diagnóstico , Displasia Ectodérmica/patologia , Feminino , Humanos , Ceratodermia Palmar e Plantar/patologia , Masculino , Pessoa de Meia-Idade , Doenças da Unha/genética , Unhas Malformadas/genética , Paquioníquia Congênita/diagnóstico , Paquioníquia Congênita/genética , Polimorfismo Genético , Adulto Jovem
15.
Pediatr Dermatol ; 36(3): 372-376, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30793783

RESUMO

CEDNIK (CErebral Dysgenesis, Neuropathy, Ichthyosis, and Keratoderma) syndrome is a neuroichthyotic syndrome characterized by a constellation of clinical features including severe developmental retardation, microcephaly, and facial dysmorphism. Here, we report the first case of CEDNIK syndrome from India presenting with characteristic clinical features and harboring a novel mutation of SNAP29 gene.


Assuntos
Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/patologia , Mutação/genética , Síndromes Neurocutâneas/genética , Síndromes Neurocutâneas/patologia , Proteínas Qb-SNARE/genética , Proteínas Qc-SNARE/genética , Feminino , Humanos , Índia , Lactente
17.
J Cutan Pathol ; 46(1): 74-79, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30294802

RESUMO

Collagenous and elastotic marginal plaques of the hand (CEMPH) is a rare, chronic keratoderma characterized by hyperkeratotic linear plaques located along the radial and ulnar aspects of the hands bilaterally. As an isolated finding, CEMPH occurs secondarily to chronic trauma and photodamage. Herein, CEMPH is described as a manifestation of alkaptonuria (AKU). In addition to keloidal collagen, ochronotic fibers and fragmented, thickened elastic fibers were observed. Additionally, mucin deposition-not previously described in this clinical context-was also identified. Given their overlapping clinicopathologic features, CEMPH due to AKU should be distinguished from the acquired variant as well as acrokeratoelastoidosis.


Assuntos
Alcaptonúria , Tecido Elástico , Mãos/patologia , Ceratodermia Palmar e Plantar , Pele , Alcaptonúria/diagnóstico , Alcaptonúria/metabolismo , Alcaptonúria/patologia , Tecido Elástico/metabolismo , Tecido Elástico/patologia , Feminino , Humanos , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/metabolismo , Ceratodermia Palmar e Plantar/patologia , Pessoa de Meia-Idade , Pele/metabolismo , Pele/patologia
19.
JAMA Dermatol ; 155(2): 216-220, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30484821

RESUMO

Importance: Development of transient palmoplantar keratoderma (PPK) with bullous pemphigoid (BP) has only been described in 2 isolated case reports. The clinical significance and the pathophysiologic mechanisms of this association are unknown. Objective: To examine the clinical characteristics and immunological profile of patients with BP who develop transient PPK and analyze therapeutic options and outcomes. Design, Setting, and Participants: In this case series, patients with BP who developed acquired, transient PPK, and were treated at a single institution from January 1, 2015, through December 31, 2017, were studied. Main Outcomes and Measures: Clinical and immunological activity of BP, treatment administrated before and after PPK appearance, and patient outcomes. Results: Six patients with BP and transient PPK were identified and included in the study. There were 5 women and 1 man with a mean age of 72 years. At baseline, all patients had a generalized, multibullous BP and high serum anti-BP180 antibodies (mean, 130 U/mL; range, 73-150), whereas anti-BP230 antibodies were elevated in only 1 case. The PPK appeared a mean 6.2 (range, 2-12) months after BP diagnosis, following a prolonged period of disease activity with recurrent flares. When the PPK occurred, BP was uncontrolled on therapy (mean Bullous Pemphigoid Disease Activity Index [BPDAI] score, 57; range, 34-105; mean anti-BP180 antibodies titer, 122 U/mL; range, 81-150). On administration of additional systemic immunosuppressive therapies, the PPK healed progressively in a mean 4.3 months (range, 2-9), along with BP clinical remission in 4 of 6 patients. No relationship was found between PPK occurrence and anti-BP180/230 antibodies profiles. In contrast, blister fluids collected at the time of PPK displayed a much higher level of interleukin 1ß (IL-1ß) compared with those collected in the absence of PKK. Expression of IL-17A, IL-17F, and IL-22 was also enhanced in the blister fluid of patients with BP who had PPK. Conclusions and Relevance: To our knowledge, this is the first report of 6 cases of BP with transient PPK with extensive immunological investigation. The PPK appeared after a prolonged period of clinical BP activity punctuated with recurrent relapses, was transient, and healed after BP control with additional immunosuppressive therapy. Enhanced expression of a particular cytokine panel in the blister fluid at time of PPK could support keratinocyte proliferation as described in patients with psoriasis. Transient PPK could represent a clinical marker of severe, treatment-resistant BP.


Assuntos
Ceratodermia Palmar e Plantar/epidemiologia , Ceratodermia Palmar e Plantar/imunologia , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/epidemiologia , Penfigoide Bolhoso/imunologia , Fatores Etários , Idoso , Autoanticorpos/sangue , Autoantígenos/imunologia , Biomarcadores/sangue , Estudos de Coortes , Comorbidade , Feminino , França , Humanos , Incidência , Interleucina-17/imunologia , Ceratodermia Palmar e Plantar/patologia , Masculino , Pessoa de Meia-Idade , Penfigoide Bolhoso/patologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Centros de Atenção Terciária
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