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5.
Actas Dermosifiliogr ; 110(4): 273-278, 2019 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30660327

RESUMO

Incontinentia pigmenti (Bloch-Sulzberger syndrome) is a rare neuroectodermal dysplasia. It is an X-linked dominant disorder caused by mutations in the IKBKG/NEMO gene on Xq28. Approximately 80% of patients have a deletion of exons 4 to 10. Incontinentia pigmenti has an estimated incidence of 0.7 cases per 100,000 births. In hemizygous males, it is usually lethal, while in females, it has a wide spectrum of clinical manifestations. Incontinentia pigmenti is a multisystemic disease that invariably features skin changes. These changes are the main diagnostic criteria and they evolve in 4 stages, in association with other abnormalities affecting the central nervous system, eyes, teeth, mammary glands, hair, nails, skin, and other parts of the body. The aim of this brief review is to highlight the clinical features of this genodermatosis and underline the importance of case-by-case interdisciplinary management, including genetic counseling.


Assuntos
Incontinência Pigmentar , Diagnóstico Diferencial , Gerenciamento Clínico , Feminino , Genes Ligados ao Cromossomo X , Genótipo , Humanos , Quinase I-kappa B/deficiência , Quinase I-kappa B/fisiologia , Incontinência Pigmentar/epidemiologia , Incontinência Pigmentar/genética , Incontinência Pigmentar/patologia , Incontinência Pigmentar/terapia , Masculino , Especificidade de Órgãos , Fenótipo , Medicina de Precisão , Deleção de Sequência , Pele/patologia
6.
J Clin Invest ; 129(2): 583-597, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30422821

RESUMO

X-linked dominant incontinentia pigmenti (IP) and X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) are caused by loss-of-function and hypomorphic IKBKG (also known as NEMO) mutations, respectively. We describe a European mother with mild IP and a Japanese mother without IP, whose 3 boys with EDA-ID died from ID. We identify the same private variant in an intron of IKBKG, IVS4+866 C>T, which was inherited from and occurred de novo in the European mother and Japanese mother, respectively. This mutation creates a new splicing donor site, giving rise to a 44-nucleotide pseudoexon (PE) generating a frameshift. Its leakiness accounts for NF-κB activation being impaired but not abolished in the boys' cells. However, aberrant splicing rates differ between cell types, with WT NEMO mRNA and protein levels ranging from barely detectable in leukocytes to residual amounts in induced pluripotent stem cell-derived (iPSC-derived) macrophages, and higher levels in fibroblasts and iPSC-derived neuronal precursor cells. Finally, SRSF6 binds to the PE, facilitating its inclusion. Moreover, SRSF6 knockdown or CLK inhibition restores WT NEMO expression and function in mutant cells. A recurrent deep intronic splicing mutation in IKBKG underlies a purely quantitative NEMO defect in males that is most severe in leukocytes and can be rescued by the inhibition of SRSF6 or CLK.


Assuntos
Displasia Ectodérmica , Mutação da Fase de Leitura , Quinase I-kappa B , Incontinência Pigmentar , Íntrons , Displasia Ectodérmica/genética , Displasia Ectodérmica/metabolismo , Displasia Ectodérmica/patologia , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Quinase I-kappa B/deficiência , Quinase I-kappa B/metabolismo , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/metabolismo , Síndromes de Imunodeficiência/patologia , Incontinência Pigmentar/genética , Incontinência Pigmentar/metabolismo , Incontinência Pigmentar/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino
11.
J Dermatol ; 45(1): 100-103, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28791733

RESUMO

Incontinentia pigmenti (IP) is an X-linked genodermatosis affecting the skin and other sites, including the teeth, nails, hair, eyes and nervous system defects in female patients. Generally lethal in males, there are only a few known cases of males surviving this condition. Nuclear factor (NF)-κB essential modulator (NEMO), also known as inhibitor of kappa light polypeptide gene enhancer in B cells, kinase gamma (IKBKG), constitutes an essential activator of NF-κB. Over 80% of female patients with IP carry a common deletion mutation involving exons 4-10 of the IKBKG/NEMO gene. We present the case of a male infant (XY) with IP with no concomitant complications. Polymerase chain reaction (PCR) assay showed that the exon 4-10 deletion band was significantly stronger in the skin sample than in blood. Subsequently, long-range PCR was performed periodically to confirm the spontaneous regression of mutant cells from his blood. Over a period of 6 years, the 2.6-kb mutant band gradually became weaker, but we did not confirm complete regression. Our patient was a healthy, 8-year-old male child with no complications despite the presence of a 2.6-kb mutant band in his blood. Further follow up is necessary to assess for complications that may develop later.


Assuntos
Quinase I-kappa B/genética , Incontinência Pigmentar/genética , Humanos , Incontinência Pigmentar/patologia , Recém-Nascido , Masculino , Remissão Espontânea , Pele/patologia
14.
Indian J Pathol Microbiol ; 60(3): 424-426, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28937389

RESUMO

Incontinentia pigmenti (IP) is a rare X-linked dominant disorder, in which skin lesions distributed along Blaschko's lines appear shortly after birth. Early lesions which are erythematous/bullous evolve over time into warty lesions, hyperpigmented swirls/macules, and atrophic hypopigmented streaks. Clinical features are heterogeneous. Abnormalities of the teeth, nails, hair, eyes, central nervous system, and breast may also be present. While intelligence is generally normal, varied degrees of intellectual disability/developmental delay have been reported. Lifespan is normal. IP is associated with mutations of the inhibitor of kappa light polypeptide gene enhancer in B cell, kinase gamma (IKBKG) gene on chromosome Xq28. This gene is involved in the activation of nuclear factor kappa B which protects cells against apoptosis; therefore, cells with IKBKG mutations are extremely susceptible to apoptosis. X-linked dominant disorders are lethal to male fetuses. Males who survive with IP either have mosaicism or an additional X chromosome (Klinefelter syndrome). We present a 22-month-old boy with IP and Klinefelter syndrome.


Assuntos
Incontinência Pigmentar/complicações , Incontinência Pigmentar/diagnóstico , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/diagnóstico , Pré-Escolar , Humanos , Quinase I-kappa B/genética , Incontinência Pigmentar/patologia , Síndrome de Klinefelter/patologia , Masculino
15.
Pediatr Dermatol ; 34(4): e203-e204, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28414858

RESUMO

We report the case of a 17-year-old girl with incontinentia pigmenti who developed multiple large hyperkeratotic tumors within Blaschkoid hyperpigmented patches on her left leg. Biopsy demonstrated an endoexophytic nodule with irregular invaginations of keratinizing squamous epithelium and a central keratin-filled crater, consistent with keratoacanthoma-like lesions of incontinentia pigmenti. The tumors were successfully treated with intralesional methotrexate.


Assuntos
Imunossupressores/administração & dosagem , Incontinência Pigmentar/tratamento farmacológico , Ceratoacantoma/patologia , Metotrexato/administração & dosagem , Adolescente , Biópsia , Feminino , Humanos , Incontinência Pigmentar/patologia , Pele/patologia
18.
Hautarzt ; 68(2): 149-152, 2017 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-27576549

RESUMO

In this article we present the case of a 2-day-old newborn girl in good general condition, with herpetic arranged pustules on the skin of her whole body. The case highlights the importance of a detailed diagnostic workup for newborns with pustular skin disease. Especially to differentiate between the diagnosis of incontinentia pigmenti and a congenital herpes infection.


Assuntos
Herpes Simples/diagnóstico , Herpes Simples/patologia , Incontinência Pigmentar/diagnóstico , Incontinência Pigmentar/patologia , Dermatopatias Virais/diagnóstico , Dermatopatias Virais/patologia , Dermatopatias Virais/virologia , Diagnóstico Diferencial , Medicina Baseada em Evidências , Feminino , Herpes Simples/virologia , Humanos , Incontinência Pigmentar/virologia , Recém-Nascido , Doenças do Recém-Nascido
20.
Dermatol Online J ; 22(6)2016 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-27617597

RESUMO

Linear vesicles or papules in a newborn can be a presenting sign of incontinentia pigmenti (IP). In this report, we present two cases of neonates with cutaneous manifestations of incontinentia pigmenti. In one case, mild peripheral eosinophilia was noted. No extra-cutaneous manifestations were noted otherwise in both cases after complete ophthalmological and neurological evaluations. These cases serve as a reminder for clinicians to consider IP in newborns presenting with linear vesicles or papules.


Assuntos
Incontinência Pigmentar/patologia , Dermatoses da Perna/patologia , Feminino , Humanos , Incontinência Pigmentar/diagnóstico , Recém-Nascido , Dermatoses da Perna/diagnóstico
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