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1.
Mol Genet Genomic Med ; 11(3): e2120, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36479642

RESUMO

BACKGROUND: Biallelic pathogenic variants in the neuroblastoma-amplified sequence (NBAS) gene manifest in a broad spectrum of disorders, including, but not limited to recurrent acute liver failure, skeletal dysmorphism, susceptibility to infections, and SOPH syndrome with its cardinal symptoms of short stature, optic atrophy, and Pelger-Huët anomaly. We aimed to present clinical and genetic characteristics of two sisters (20 and 15 years old) who were diagnosed with optic atrophy and cone dystrophy in childhood. Genome sequencing revealed two novel variants in NBAS in compound heterozygous state in both sisters, namely a 1-bp deletion predicted to result in a premature termination codon (c.5104del; p.(Met1702*)), and a non-canonical splice site variant of unclear significance (c.886-5T>A; p.?). RESULTS: Clinical examination and history revealed cone dystrophy, optic atrophy, and Pelger-Huët anomaly, but no short stature, recurrent acute liver failure, or susceptibility to infections. RNA analysis revealed that the c.886-5T>A variant results in two aberrant transcripts that are predicted to lead to in frame amino acid changes in the ß-propeller region of the protein. CONCLUSION: We hypothesize that the phenotype of our subjects, which appears to be at the end of the spectrum of NBAS-related disorders, could be explained by residual protein function mediated by the non-canonical splice site variant c.886-5T>A. Our study contributes to the existing knowledge on the genotypic and phenotypic spectrum of NBAS-related disorders.


Assuntos
Distrofia de Cones , Nanismo , Falência Hepática Aguda , Neuroblastoma , Atrofia Óptica , Anomalia de Pelger-Huët , Humanos , Anomalia de Pelger-Huët/diagnóstico , Anomalia de Pelger-Huët/genética , Anomalia de Pelger-Huët/patologia , Atrofia Óptica/genética , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/genética , Nanismo/genética , Fenótipo
2.
Int J Hematol ; 116(5): 807-811, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35760941

RESUMO

Capnocytophaga canimorsus is a Gram-negative bacillus of the commensal flora of dogs and cats that can cause infections in humans through bites, scratches or contact with oral secretions. It can be difficult to identify in clinical microbiology laboratories because of the need for specific culture media. We present the case of a patient with no relevant medical history who was admitted with septic shock, where blood smear examination was crucial for the etiologic diagnosis of Capnocytophaga canimorsus infection. The patient was also diagnosed Pelger-Huët anomaly, a condition causing a defect in neutrophil chemotaxis, which may have contributed to the severity of the infection.


Assuntos
Infecções por Bactérias Gram-Negativas , Anomalia de Pelger-Huët , Choque Séptico , Humanos , Capnocytophaga , Meios de Cultura , Infecções por Bactérias Gram-Negativas/etiologia , Anomalia de Pelger-Huët/diagnóstico , Choque Séptico/diagnóstico , Choque Séptico/etiologia
10.
J Hum Genet ; 64(7): 609-616, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31015584

RESUMO

Individuals affected with autosomal recessive cutis laxa type 2B and 3 usually show translucent skin with visible veins and abnormal elastic fibers, intrauterine and/or postnatal growth restriction and a typical triangular facial gestalt. Here we describe three unrelated individuals in whom such a cutis laxa syndrome was suspected, especially after electron microscopy revealed immature and less dense dermal elastic fibers in one of them. However, one of these children also displayed optic atrophy and two hypogammaglobulinemia. All had elevated liver enzymes and acute liver failure during febrile episodes leading to early demise in two of them. The only surviving patient had been treated with immunoglobulins. Through exome sequencing we identified mutations in NBAS, coding for a protein involved in Golgi-to-ER transport. NBAS deficiency causes several rare conditions ranging from isolated recurrent acute liver failure to a multisystem disorder mainly characterized by short stature, optic nerve atrophy and Pelger-Huët anomaly (SOPH). Since we subsequently verified Pelger-Huët anomaly in two of the patients the diagnosis SOPH syndrome was unequivocally proven. Our data show that SOPH syndrome can be regarded as a differential diagnosis for the progeroid forms of cutis laxa in early infancy and that possibly treatment of the hypogammaglobulinemia can be of high relevance for the prognosis.


Assuntos
Transtornos do Crescimento/diagnóstico , Proteínas de Neoplasias/genética , Doenças do Nervo Óptico/diagnóstico , Anomalia de Pelger-Huët/diagnóstico , Agamaglobulinemia/sangue , Agamaglobulinemia/fisiopatologia , Cútis Laxa/diagnóstico , Cútis Laxa/genética , Cútis Laxa/patologia , Diagnóstico Diferencial , Tecido Elástico/ultraestrutura , Transtornos do Crescimento/genética , Transtornos do Crescimento/patologia , Humanos , Lactente , Fígado/enzimologia , Fígado/patologia , Masculino , Doenças do Nervo Óptico/genética , Doenças do Nervo Óptico/patologia , Anomalia de Pelger-Huët/genética , Anomalia de Pelger-Huët/patologia , Progéria/diagnóstico , Progéria/genética , Pele/patologia , Síndrome , Sequenciamento do Exoma , Adulto Jovem
11.
BMJ Case Rep ; 20182018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29545424

RESUMO

A 70-year-old man visited our emergency department, whose laboratory test results revealed leucocytosis, anaemia, thrombocytopenia and high levels of serum lactate dehydrogenase. In addition, the peripheral blood smear revealed neutrophilic granulocytes with nuclear hypolobation (pseudo-Pelger-Hüet anomaly), hypogranulation and no myeloperoxidase reactivity. Genetic testing of the peripheral blood sample was as follows: G-band, 46XY,t(9;22)(q34;q11.2) (20/20); fluorescence in situ hybridisation BCR/ABL fusion signal, 97%; and analysis of exons 5-9 of the p53 gene, mutation (Pro72Arg) in exon 4 protein. On the basis of these findings, the patient was diagnosed with chronic myelogenous leukaemia (CML) in chronic phase with a p53 mutation and treated with hydroxyurea, dasatinib and nilotinib. Neutrophilic granulocytes with the anomalies were no longer observed after achieving cytogenetic remission. To the best of our knowledge, this is the first report of CML case with the anomalies, in which a p53 mutation without chromosome 17 abnormalities was identified.


Assuntos
Granulócitos/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Anomalia de Pelger-Huët/diagnóstico , Idoso , Diagnóstico Diferencial , Humanos , Hibridização in Situ Fluorescente , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Masculino , Anomalia de Pelger-Huët/sangue , Anomalia de Pelger-Huët/complicações
12.
Pediatrics ; 139(1)2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28031453

RESUMO

Acute liver failure (ALF) is a life-threatening condition in the absence of preexisting liver disease in children. The main clinical presentation comprises hepatic dysfunction, elevated liver biochemical values, and coagulopathy. The etiology of ALF remains unclear in most affected children; however, the recent identification of mutations in the neuroblastoma amplified sequence (NBAS) gene in autosomal recessively inherited ALF has shed light on the cause of a subgroup of fever-triggered pediatric ALF episodes. Previously, biallelic mutations in NBAS have been reported to be associated with a syndrome comprising short stature, optic atrophy, and Pelger-Huët anomaly (SOPH) specifically occurring in the Yakut population. No hepatic phenotype has been observed in individuals with this disorder who all carry the homozygous NBAS founder mutation c.5741G>A [p.(Arg1914His)]. We present the case of a 4-year-old girl with the cardinal features of SOPH syndrome: characteristic facial dysmorphism, postnatal growth retardation, delay of bone age, slender long bones, optic atrophy, and Pelger-Huët anomaly. During the first 2 years of her life, a series of infections with episodes of fever were accompanied by elevated liver enzyme levels, but hyperammonemia, hypoglycemia, coagulopathy, or encephalopathy suggestive of acute and severe liver disease were never observed. Whole exome sequencing in the patient revealed compound heterozygosity of the 2 NBAS variants, p.(Arg1914His) and p.(Glu943*). This case highlights the variability of clinical presentation associated with NBAS deficiency. Absence of severe liver problems in this case and SOPH-affected Yakut subjects suggests that individuals carrying the NBAS missense mutation p.(Arg1914His) are less susceptible to developing ALF.


Assuntos
Deficiências do Desenvolvimento/genética , Nanismo/diagnóstico , Nanismo/genética , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/genética , Proteínas de Neoplasias/genética , Atrofia Óptica/genética , Anomalia de Pelger-Huët/diagnóstico , Anomalia de Pelger-Huët/genética , Fenótipo , Alelos , Pré-Escolar , Análise Mutacional de DNA , Deficiências do Desenvolvimento/diagnóstico , Exoma/genética , Feminino , Triagem de Portadores Genéticos , Humanos , Mutação de Sentido Incorreto/genética , Proteínas de Neoplasias/deficiência , Atrofia Óptica/diagnóstico , Síndrome
13.
Cytometry B Clin Cytom ; 92(6): 541-549, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-27684937

RESUMO

The nuclear morphology of neutrophils depends on different endogenous and exogenous factors, which can lead to hypo- or hypersegmentation of the normally 2-4 segmented nucleus. Hyposegmentation can be due to mutations in the LBR-gene (Pelger-Huët-Anomaly) or can be induced, for example, by colchicine treatment. The range of this phenotypic variation is known as "norm of reaction," which can be of major relevance for clinical diagnosis and therapeutic intervention. In this project, we studied the norm of reaction in 26 subjects with 0-3 wild type LBR alleles. In addition, the phenotypic variation was analyzed in 3 patients with Familial Mediterranean Fever (FMF), before and after colchicine treatment. We measured the phenotype nuclear segmentation of neutrophils based on two conventional qualitative methods, the "rule of threads" and the "rule of thirds." In addition, we tested a morphometric quantitative approach, the "circularity index." The circularity index was superior in cases with hyposegmentation; the rule of thirds with respect to hypersegmentation. Approximately 65% of the observed phenotypic variance was explainable by the number of LBR wild type alleles. The gene-dosage effect followed a non-additive, hysteresis-like characteristic with lower and upper plateaus. Colchicine treatment had a clear, although minor phenotypic effect compared to the number of LBR wild type genes or the mutation type. Thus, the nuclear morphology of granulocytes and its norm of reaction can be regarded as an excellent model both for detailing the interplay between endogenous and exogenous factors and for clinical diagnostic purposes. © 2016 International Clinical Cytometry Society.


Assuntos
Núcleo Celular/efeitos dos fármacos , Colchicina/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Neutrófilos/efeitos dos fármacos , Anomalia de Pelger-Huët/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/genética , Adolescente , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Pré-Escolar , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/metabolismo , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Masculino , Mutação , Neutrófilos/metabolismo , Neutrófilos/ultraestrutura , Anomalia de Pelger-Huët/diagnóstico , Anomalia de Pelger-Huët/genética , Anomalia de Pelger-Huët/metabolismo , Fenótipo , Cultura Primária de Células , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptor de Lamina B
15.
J Pediatr ; 173: 238-241.e1, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27039225

RESUMO

In the treatment of Kawasaki disease, resistance to high-dose immunoglobulin intravenous (IGIV) can occur. The neutrophil morphology analyses in 17 patients revealed that transient pseudo-Pelger-Huët anomaly was more frequently detected in the IGIV-resistant group. This finding may aid the prediction of IGIV resistance.


Assuntos
Resistência a Medicamentos , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Anomalia de Pelger-Huët/diagnóstico , Pré-Escolar , Feminino , Humanos , Masculino , Anomalia de Pelger-Huët/complicações , Estudos Retrospectivos
16.
Ann Biol Clin (Paris) ; 74(1): 110-6, 2016.
Artigo em Francês | MEDLINE | ID: mdl-26878615

RESUMO

An acute myeloid leukemia was diagnosed in a 53-year-old female patient. She received an allogeneic stem cell transplant. After this transplant, some neutrophils with hyposegmented nucleus and abnormal chromatin clumping appeared in the peripheral blood, and their number gradually increased. The hypothesis of early relapse after transplant was ruled out and drug-related anomaly was suspected. The authors discuss about morphological features of constitutional and acquired Pelger-Huët anomaly. In the patient reported here, ciclosporine seemed to be involved in the phenomenon, as the morphological anomaly of the neutrophils gradually decreased after the drug was discontinued.


Assuntos
Cromatina/patologia , Ciclosporina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Granulócitos/patologia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Anomalia de Pelger-Huët/etiologia , Cromatina/efeitos dos fármacos , Cromatina/metabolismo , Diagnóstico Diferencial , Feminino , Granulócitos/efeitos dos fármacos , Granulócitos/metabolismo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/sangue , Pessoa de Meia-Idade , Anomalia de Pelger-Huët/induzido quimicamente , Anomalia de Pelger-Huët/diagnóstico , Recidiva , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos
18.
Int J Hematol ; 102(1): 129-33, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25749661

RESUMO

Pseudo-Pelger-Huët anomaly (PHA) refers to mono- or bi-lobed granulocytes, reportedly observed in patients with severe infections and inflammation or hematological malignancies including myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Dysplastic changes in granulocytes are typical manifestations in MDS and granulocytic leukemias. Here, we report the unique case of a patient found to have human granulocytic anaplasmosis (HGA), a tick-borne disease caused by Anaplasma phagocytophilum, a Gram-negative coccobacillus. This patient showed striking hematological manifestations including a large number of pseudo-PHA, a severe degree of left shift, and dysplastic granulocytes. These hematological presentations on the peripheral smear all resolved with doxycycline treatment, implying that the changes were most likely reactive manifestations secondary to HGA, rather than underlying hematological malignancies such as MDS or AML.


Assuntos
Anaplasmose/diagnóstico , Granulócitos/patologia , Anomalia de Pelger-Huët/diagnóstico , Adulto , Anaplasma phagocytophilum , Anaplasmose/tratamento farmacológico , Anaplasmose/microbiologia , Diagnóstico Diferencial , Humanos , Masculino , Neutrófilos/patologia
19.
Vet Clin Pathol ; 43(3): 337-41, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25115222

RESUMO

A 14-year-old, spayed female Domestic Shorthair cat was referred to the Purdue University Veterinary Teaching Hospital (PUVTH) for iodine 131 treatment of hyperthyroidism. Upon arrival, a biochemistry profile and a CBC were performed. Approximately 50% of the neutrophils and all the eosinophils observed were hyposegmented with a mature, condensed chromatin pattern. Nuclei had a band to "dumbbell" shape, and rarely a round shape, suggesting a Pelger-Huët anomaly or a pseudo Pelger-Huët. Based on both a negative FeLV and FIV tests, the absence of any clinical signs to support an inflammatory process, and the persistence of this granulocytic morphology 6 months after its previous admission to the PUVTH, a diagnosis of Pelger-Huët anomaly was established in this cat.


Assuntos
Doenças do Gato/sangue , Núcleo Celular/patologia , Granulócitos/patologia , Anomalia de Pelger-Huët/veterinária , Animais , Doenças do Gato/diagnóstico , Gatos , Cromatina/patologia , Diagnóstico Diferencial , Eosinófilos/patologia , Feminino , Neutrófilos/patologia , Anomalia de Pelger-Huët/sangue , Anomalia de Pelger-Huët/diagnóstico
20.
J Perinatol ; 32(3): 238-40, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22370897

RESUMO

We observed a neonate with cleft lip and palate, 13 sets of ribs, agenesis of the corpus callosum, slightly small penis, hypoglycemia, and what initially appeared to be a marked leukocyte 'left shift' on complete blood count, but which was actually a Pelger-Huët anomaly. A chromosomal microdeletion was identified at1q41-42.12.


Assuntos
Anormalidades Múltiplas/genética , Agenesia do Corpo Caloso/genética , Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Fenda Labial/genética , Fissura Palatina/genética , Anomalia de Pelger-Huët/diagnóstico , Adulto , Agenesia do Corpo Caloso/diagnóstico , Citogenética , Feminino , Humanos , Recém-Nascido , Análise de Sequência com Séries de Oligonucleotídeos , Anomalia de Pelger-Huët/genética
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