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Arch. argent. pediatr ; 118(3): e288-e291, jun. 2020. ilus
Artigo em Inglês, Espanhol | LILACS (Américas), BINACIS | ID: biblio-1116957


El síndrome de Pierson se caracteriza por la presencia de síndrome nefrótico congénito y microcoria bilateral. Genéticamente, este trastorno está ocasionado por mutaciones en el gen LAMB2, que codifica la cadenaß2 de la laminina. Hasta la fecha, en la bibliografía se informaron 98casos y 50mutaciones diferentes. No existen terapias específicas para el síndrome de Pierson, y el tratamiento es complementario. El pronóstico es malo por la disfunción renal progresiva y las complicaciones de la insuficiencia renal. En este artículo, se informa sobre una mutación homocigota novedosa (c.1890G>C [p.Q630H]) en el gen LAMB2 en una paciente con síndrome de Pierson que tenía un fenotipo atípico, como epidermólisis ampollosa.

Pierson syndrome is characterized by congenital nephrotic syndrome and bilateral microcoria. Genetically, mutations in the LAMB2 gene, which encodes the laminin ß2 chain, lead to this disorder. To date, 98 cases and 50 different mutations have been reported in literature. There are no specific therapies for Pierson syndrome and treatment is supportive. The prognosis is poor because of progressive impairment of renal function and complications of renal failure. We report a novel homozygous mutation (c.1890G>T, p.Q630H) in the LAMB2 gene in a patient with Pierson syndrome who had atypical phenotypic feature such as epidermolysis bullosa

Humanos , Feminino , Lactente , Mutação , Síndrome Nefrótica/diagnóstico , Turquia , Epidermólise Bolhosa , Evolução Fatal , Insuficiência Renal
Appl. cancer res ; 40(4): [1-12], 01 june 2020. ilus, tab
Artigo em Inglês | LILACS (Américas) | ID: biblio-1103878


Background: Next-generation sequencing (NGS) based assay for finding an actionable driver in non-small-cell lung cancer is a less used modality in clinical practice. With a long list of actionable targets, limited tissue, arduous single-gene assays, the alternative of NGS for broad testing in one experiment looks attractive. We report here our experience with NGS for biomarker testing in hundred advanced lung cancer patients. Methods: Predictive biomarker testing was performed using the Ion AmpliSeq™ Cancer Hotspot Panel V2 (30 tumors) and Oncomine™ Solid Tumor DNA and Oncomine™ Solid Tumor Fusion Transcript kit (70 tumors) on IonTorrent sequencing platform. Results: One-seventeen distinct aberrations were detected across 29 genes in eighty-six tumors. The most commonly mutated genes were TP53 (43% cases), EGFR (23% cases) and KRAS (17% cases). Thirty-four patients presented an actionable genetic variant for which targeted therapy is presently available, and fifty-two cases harbored non-actionable variants with the possibility of recruitment in clinical trials. NGS results were validated by individual tests for detecting EGFR mutation, ALK1 rearrangement, ROS1 fusion, and c-MET amplification. Compared to single test, NGS exhibited good agreement for detecting EGFR mutations and ALK1 fusion (sensitivity- 88.89%, specificity- 100%, Kappa-score 0.92 and sensitivity- 80%, specificity- 100%, Kappa-score 0.88; respectively). Further, the response of patients harboring tyrosine kinase inhibitor (TKI) sensitizing EGFR mutations was assessed. The progression-free-survival of EGFR positive patients on TKI therapy, harboring a concomitant mutation in PIK3CAmTOR and/or RAS-RAF-MAPK pathway gene and/or TP53 gene was inferior to those with sole-sensitizing EGFR mutation (2 months vs. 9.5 months, P = 0.015). Conclusions: This is the first study from South Asia looking into the analytical validity of NGS and describing the mutational landscape of lung cancer patients to study the impact of co-mutations on cancer biology and treatment outcome. Our study demonstrates the clinical utility of NGS testing for identifying actionable variants and making treatment decisions in advanced lung cancer

Humanos , Masculino , Feminino , Biomarcadores Tumorais , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares , Mutação
Electron. j. biotechnol ; 44: 19-24, Mar. 2020. ilus, graf
Artigo em Inglês | LILACS (Américas) | ID: biblio-1087631


BACKGROUND: Pyruvic acid (PA), a vital α-oxocarboxylic acid, plays an important role in energy and carbon metabolism. The oleaginous yeast Yarrowia lipolytica (Y. lipolytica) has considerable potential for the production of PA. An increased NaCl concentration reportedly increases the biomass and PA yield of Y. lipolytica. RESULTS: To increase the yield of PA, the NaCl-tolerant Y. lipolytica A4 mutant was produced using the atmospheric and room temperature plasma method of mutation. The A4 mutant showed growth on medium containing 160 g/L NaCl. The PA yield of the A4 mutant reached 97.2 g/L at 120 h (0.795 g/g glycerol) in a 20-L fermenter with glycerol as the sole carbon source, which was 28.9% higher than that of the parental strain. CONCLUSION: The PA yield from Y. lipolytica can be improved by increasing its NaCl tolerance.

Ácido Pirúvico/metabolismo , Yarrowia/genética , Yarrowia/metabolismo , Pressão Osmótica , Leveduras , Carbono/metabolismo , Cloreto de Sódio , Reatores Biológicos , Tolerância ao Sal/genética , Fermentação , Glicerol/metabolismo , Mutação
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781307


OBJECTIVE@#To analyze variants of PRRT2 gene in two children with paroxysmal kinesigenic dyskinesia.@*METHODS@#Genomic DNA of the two children and their parents was extracted from peripheral venous blood samples. All exons and their flanking regions of the PRRT2 gene were subjected to PCR and Sanger sequencing.@*RESULTS@#The two children were found to respectively harbor a c.282dupA and a c.715_716dupCC variant in exon 2 of the PRRT2 gene, which were both inherited from their mothers. Pooling together their frequencies in general population, genetic models, related literature and impact on protein function, the two novel variants were both predicted to be pathogenic.@*CONCLUSION@#The c.282dupA and c.715_716dupCC variants probably underlie the disease in the two children.

Criança , Distonia , Genética , Feminino , Humanos , Proteínas de Membrana , Genética , Mutação , Proteínas do Tecido Nervoso , Genética
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781305


OBJECTIVE@#To detect pathogenic variant of ARSA gene in an infant with late infantile metachromatic leukodystrophy (MLD).@*METHODS@#The male proband had an onset of walking dysfunction and seizure at 28 months. Arylsulfatase A activity of his peripheral blood leucocytes was 26.9 nmol/mg.17h, and cranial MRI showed wild symmetrical demyelination. With genomic DNA extracted from his peripheral blood sample, all coding exons and splicing sites of the ARSA gene were subjected to Sanger sequencing. PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. Ucsf chimera software was used to analyze the impact of candidate variants on the secondary structure of the protein product. Impact of potential variants was also analyzed with software including PolyPhen-2, Mutation Taster, SIFT and PROVEAN. Whole-exome sequencing was carried out to identify additional variants which may explain the patient's condition.@*RESULTS@#The proband was found to harbor compound heterozygous variants of the ARSA gene [c.467G>A (p.Gly156Asp) and c.960G>A (p.Trp320*)], neither of which was reported previously. As predicted by Ucsf chimera software, the c.960G>A (p.Trp320*) variant may demolish important secondary structures including α-helix, β-strand and coil of the ARSA protein, causing serious damage to its structure and loss of function. The c.467G>A (p.Gly156Asp) variant was predicted to be "probably damaging" by PolyPhen-2, Mutation Taster and SIFT software.@*CONCLUSION@#The patient's condition may be attributed to the compound heterozygous c.467G>A (p.Gly156Asp) and c.960G>A (p.Trp320*) variants of the ARSA gene. Above results have facilitated genetic counseling and prenatal diagnosis for this family.

Cerebrosídeo Sulfatase , Genética , Éxons , Genética , Feminino , Humanos , Lactente , Leucodistrofia Metacromática , Genética , Masculino , Mutação , Genética , Gravidez , Processamento de RNA , Genética
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781304


OBJECTIVE@#To explore the genetic basis of a pedigree affected with hereditary spherocytosis.@*METHODS@#Peripheral blood samples were collected from 17 members of the pedigree. Genomic DNA of the proband was subjected to next generation sequencing. Candidate variant was validated by co-segregation analysis. pCAS2(c.5798+1G) and pCAS2(c.5798+1A) plasmids were constructed by homologous recombination and transfected into 293T cells. Reverse transcription PCR, TA cloning and Sanger sequencing were used to analyze the effect of candidate variant on splicing. Meanwhile, peripheral blood RNAs were extracted to analyze the effect of candidate variant on splicing in vivo.@*RESULTS@#The proband was found to carry a c.5798+1G>A variant of the SPTB gene. The variant has co-segregated with the phenotype in the pedigree. In vitro and in vivo splicing experiments confirmed that the mutation has significantly affected the splicing, resulting in shift of reading frame and produced a premature termination codon.@*CONCLUSION@#The novel c.5798+1G>A variant of the SPTB gene probably underlies the pathogenesis of hereditary spherocytosis in this pedigree.

Códon sem Sentido , Genética , Variação Genética , Células HEK293 , Humanos , Mutação , Genética , Linhagem , Plasmídeos , Processamento de RNA , Espectrina , Genética , Esferocitose Hereditária , Genética , Transfecção
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781303


OBJECTIVE@#To identify potential variant in a child diagnosed as infantile neuroaxonal dystrophy.@*METHODS@#Genomic DNA was extracted from peripheral blood samples from the patient and his parents and subjected to next generation sequencing. Suspected variant was verified by PCR and Sanger sequencing. Pathogenicity of the mutation was predicted by using bioinformatic software including SIFT and PolyPhen-2.@*RESULTS@#The child was found to carry compound heterozygous variations c.668C>A (p.Pro223Gln) and c.2266C>T (p.Gln756Ter) of the PLA2G6 gene, which were respectively inherited from his father and mother. c.2266C>T has changed codon 756 (glutamine) into a stop codon, resulting premature termination of peptide chain synthesis. c.2266C>T has not been reported previously and was predicted to be harmful.@*CONCLUSION@#The compound variants of c.668C>A (p.Pro223Gln) and c.2266C>T (p.Gln756Ter) of the PLA2G6 gene probably underlies the disease in the child. Above finding has enriched the variant spectrum of the PLA2G6 gene.

Criança , Fosfolipases A2 do Grupo VI , Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Distrofias Neuroaxonais , Genética
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781300


OBJECTIVE@#To explore hematological and genotypic characteristics of patients with hemoglobin E (Hb E) disorders from Yunnan Province.@*METHODS@#One hundred individuals with Hb E disorders indicated by high performance liquid chromatography (HPLC) were subjected to genetic testing through multiple gap-PCR and reverse dot-blotting analysis.@*RESULTS@#All patients were found to harbor a mutation to the 26th codon of the β -globin chain (HBB: c.79G>A). Ninety patients were heterozygotes, and 10 co-inherited c.79G>A and an α -thalassemia mutation (7 α α /-α, 2 α α /-- and 1 -α /-α). Hematological characteristics of the heterozygotes were: Hb A2 (26.02±3.64)%, Hb F(1.35±1.25)%, MCV(78.83±4.68) fl, MCH(26±1.54) pg, MCHC (329.65±10.73) g/L, HGB (141.08±16.53) g/L, while that of the co-inherited cases was decided by the type of α -thalassemia mutation.@*CONCLUSION@#Hb E can be effectively detected by HPLC. The type of α -thalassemia mutations will determine hematological features of co-inherited cases. Hb E disorders may be missed by relying only on routine blood test upon prenatal screening.

China , Feminino , Genótipo , Hemoglobina E , Genética , Humanos , Mutação , Gravidez , Talassemia alfa , Genética , Globinas beta , Genética
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781298


OBJECTIVE@#To explore the genetic basis of a patient featuring global developmental delay, intellectual disability, cleft palate, seizures and hypotonia.@*METHODS@#Clinical examination and laboratory tests were carried out. Peripheral blood samples were obtained from the patient and his parents. Whole genomic DNA was extracted and subjected to next generation sequencing. Candidate variation was analyzed by using bioinformatic software and validated by Sanger sequencing.@*RESULTS@#The proband was found to carry a heterozygous c.2117T>C (p.Leu706Pro) variant of the NEDD4L gene, which was a de novo variant validated by Sanger sequencing and predicted to be likely pathogenic according to the American College of Medical Genetics Guidelines.@*CONCLUSION@#The heterozygous variant of c.2117T>C (p.Leu706Pro) of the NEDD4L gene probably underlies the disorders in the patient.

Testes Genéticos , Heterozigoto , Humanos , Deficiência Intelectual , Genética , Masculino , Mutação , Ubiquitina-Proteína Ligases Nedd4 , Genética , Heterotopia Nodular Periventricular , Genética
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781293


OBJECTIVE@#To explore the molecular basis for a pedigree affected with May-Hegglin anomaly (MHA).@*METHODS@#Peripheral blood samples were collected and subjected to DNA extraction. Exons 1, 10, 16, 24, 25, 26, 30, 31, 33, 38 and 40 and flanking sequences of the MYH9 gene were subjected to PCR amplification and Sanger sequencing. Changes in protein expression were determined by an indirect immunofluorescence assay. Platelet aggregation function of the proband was assessed by thromboelastogram.@*RESULTS@#The proband and his second son both carried a heterozygous 5521G>A (GAG to AAG) missense variant in exon 38 of the MYH9 gene, leading to p.Glu1841Lys substitution at position 1841 of amino acid sequence. Immunofluorescence showed inclusions containing NMMHC-II A. Thromboelastogram suggested enhanced platelet aggregation function of the proband.@*CONCLUSION@#The c.5521G>A variant of MYH9 gene has co-segregated with the phenotype of MHA in this pedigree. To assess the aggregation function of platelet by thromboelastogram can predict the risk of bleeding in MHA patients.

Perda Auditiva Neurossensorial , Genética , Humanos , Masculino , Mutação , Cadeias Pesadas de Miosina , Genética , Linhagem , Trombocitopenia , Genética
Rev. bras. cir. plást ; 34(4): 571-575, oct.-dec. 2019. ilus
Artigo em Inglês, Português | LILACS (Américas) | ID: biblio-1047934


O presente estudo objetiva relatar a técnica do retalho toracoabdominal pós-mastectomia por tumor localmente avançado em paciente com mutação de BRCA1. Foi realizada a mastectomia com ressecção de quase todo o músculo peitoral maior à esquerda, com linfonodectomia axilar homolateral e reconstrução do grande defeito da parede torácica com retalho toracoabdominal fasciocutâneo, baseado nas artérias intercostais posteriores.

This case report describes the application of the thoracoabdominal flap technique after locally advanced tumor mastectomy in a patient with breast cancer 1 (BRCA1) mutation. The mastectomy included resection of nearly the entire left pectoralis major muscle, with homolateral axillary lymphadenectomy and reconstruction of the large chest wall defect with a fasciocutaneous thoracoabdominal flap based on the posterior intercostal arteries.

Humanos , Feminino , Adulto , História do Século XXI , Pacientes , Retalhos Cirúrgicos , Mama , Neoplasias da Mama , Procedimentos Cirúrgicos Reconstrutivos , Oncologia Cirúrgica , Mutação , Retalhos Cirúrgicos/transplante , Mama/cirurgia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Oncologia Cirúrgica/métodos , Mutação/ética
Arch. argent. pediatr ; 117(6): 684-687, dic. 2019. tab
Artigo em Espanhol | LILACS (Américas), BINACIS | ID: biblio-1051382


La xerocitosis hereditaria es un desorden poco frecuente causado por defectos en la permeabilidad eritrocitaria, que se caracteriza por anemia hemolítica de gravedad variable y sobrecarga de hierro. El diagnóstico suele ser tardío y confundirse con otras anemias hemolíticas, lo que puede llevar a indicaciones de procedimientos, como la esplenectomía, contraindicados en estos pacientes. Se reportan las características clínicas, hematológicas y moleculares de dos pacientes pediátricos no relacionados con diagnóstico de xerocitosis hereditaria. Ambos presentaban eritrocitos deshidratados con alta concentración de hemoglobina corpuscular media, frotis no patognomónico, marcadores de hemólisis y una curva de fragilidad osmótica resistente. El diagnóstico se confirmó por la secuenciación del gen PIEZO.Se resalta la importancia de reconocer la causa de la anemia hemolítica para dar un enfoque terapéutico preciso y dar adecuado consejo genético

Hereditary xerocytosis is a rare disorder caused by defects of red blood cell permeability that are characterized by hemolytic anemia of variable degree and iron overload. Diagnosis is usually late and confused with other hemolytic anemias, which can lead to procedural indications, such as splenectomy, contraindicated in these patients. We report the clinical, haematological, and molecular characteristics of two patients from two unrelated families affected by hereditary xerocytosis. Both patients had dehydrated erythrocytes with a high concentration of mean corpuscular hemoglobin, non-pathognomonic smears, markers of hemolysis and a resistant osmotic fragility curve. The diagnosis was confirmed by the sequencing of the PIEZO gene. We emphasize the importance of recognizing the cause of hemolytic anemia to give an accurate therapeutic approach and give adequate genetic counseling.

Humanos , Masculino , Feminino , Criança , Adolescente , Hidropisia Fetal/diagnóstico , Anemia Hemolítica Congênita/diagnóstico , Mutação , Linhagem , Hemoglobinas/análise , Sobrecarga de Ferro , Índices de Eritrócitos , Anemia Hemolítica Congênita/complicações , Anemia Hemolítica Congênita/genética , Anemia Hemolítica Congênita/sangue , Icterícia Neonatal
Rev. Paul. Pediatr. (Ed. Port., Online) ; 37(4): 520-524, Oct.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS (Américas) | ID: biblio-1041362


ABSTRACT Objective: To describe the case of a patient with central congenital hypothyroidism (CCH) due to a recurrent mutation in the TSHB gene, as well as to conduct a genetic study of his family. Case description: It is presented a case report of a 5-month-old boy with a delayed diagnosis of isolated CCH in whom the molecular analysis was performed 12 years later and detected a recurrent mutation (c.373delT) in TSHB gene. The parents and sister were carriers of the mutant allele. Comments: The c.373delT mutation has previously been reported in patients from Brazil, Germany, Belgium, United States, Switzerland, Argentina, France, Portugal, United Kingdom and Ireland. In summary, our case and other ones reported in the literature support the theory that this mutation may be a common cause of isolated TSH deficiency. Isolated TSH deficiency is not detected by routine TSH-based neonatal screening, representing a clinical challenge. Therefore, when possible, molecular genetic study is indicated. Identification of affected and carriers allows the diagnosis, treatment and adequate genetic counseling.

RESUMO Objetivo: Descrever o caso de um paciente com hipotireoidismo congênito central (HCC) por conta de uma mutação recorrente no gene TSHB, bem como realizar um estudo genético de sua família. Descrição do caso: Relato de caso de um menino de 5 meses de idade com diagnóstico tardio de HCC isolado, em quem a análise molecular foi realizada 12 anos depois e detectou uma mutação recorrente (c.373delT) no gene TSHB. Os pais e a irmã eram portadores do alelo mutante. Comentários: A mutação c.373delT já foi relatada em pacientes do Brasil, da Alemanha, da Bélgica, dos Estados Uinidos, da Suíça, da Argentina, da França, de Portugal, do Reino Unido e da Irlanda. Em resumo, nosso caso e outros relatados na literatura reforçam a teoria de que essa mutação pode ser uma causa comum de deficiência isolada de TSH. A deficiência isolada de TSH não é detectada na triagem neonatal com base na dosagem de TSH, representando um desafio clínico. Portanto, quando possível, o estudo genético molecular é indicado. A identificação dos afetados e dos portadores permite o diagnóstico, o tratamento e o aconselhamento genético adequado.

Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Criança , Adulto , Triagem Neonatal , Hipotireoidismo Congênito/diagnóstico , Tireotropina Subunidade beta/genética , Diagnóstico Tardio , Mutação , Marcadores Genéticos , Hipotireoidismo Congênito/genética
Horiz. méd. (Impresa) ; 19(4): 74-83, Dic. 2019. ilus
Artigo em Espanhol | LILACS (Américas), LIPECS | ID: biblio-1048874


En los últimos años, el rápido desarrollo tecnológico y el mayor conocimiento de aspectos genéticos y moleculares en medicina han permitido un mejor enfoque en el entendimiento, diagnóstico y tratamiento de diversas enfermedades oncológicas. En relación con el carcinoma de pulmón, ha habido una significativa evolución desde sus primeras clasificaciones, puramente morfológicas, hasta la última del año 2015, en la que se integra información histológica, inmunofenotípica, genética molecular, clínica, y radiológica, lo que permite una mejor evaluación y manejo terapéutico de estos pacientes. En el presente artículo se hace un repaso desde las primeras clasificaciones del carcinoma de pulmón hasta la última, y se examinan los cambios más relevantes y la importancia de los hallazgos genéticos moleculares para un mejor enfoque clínico y terapéutico.

Current classification of lung carcinoma. Histological, immunophenotypic, molecular and clinical considerations ABSTRACT In recent years, the rapid technological development and the better knowledge of genetic and molecular aspects in medicine have allowed a better approach to understand, diagnose and treat various oncological diseases. Regarding lung carcinoma, there has been a remarkable evolution from the first classifications, which were purely morphological, to the last one issued in 2015. This last classification includes histological, immunophenotypic, molecular genetics, clinical and radiological information, which allows a better evaluation and therapeutic management of these patients. In the present article, the first classifications of lung carcinoma to the last one are reviewed, and the most relevant changes and the importance of the molecular genetics findings are examined for a better clinical and therapeutic approach.

Humanos , Carcinoma , Classificação , Pulmão , Mutação
An. bras. dermatol ; 94(6): 658-663, Nov.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS (Américas) | ID: biblio-1054887


Abstract Background: Palmoplantar pustulosis is considered to be a localized pustular psoriasis confined to the palms and soles. Mutation of the IL36RN gene, encoding interleukin-36 receptor antagonist (IL-36Ra), is associated with generalized pustular psoriasis, but IL36RN mutations in Chinese palmoplantar pustulosis patients have not previously been investigated. Objective: The aim of this study was to evaluate the mutation of IL36RN in Chinese patients with palmoplantar pustulosis. Methods: Fifty-one Han Chinese patients with palmoplantar pustulosis were recruited. All exons and exon-intron boundary sequences of IL36RN were amplified in polymerase chain reactions, and Sanger sequencing of the amplicons was performed. Results: Among the 51 palmoplantar pustulosis patients, four different single-base substitutions were identified in nine patients. The mutations were c.140A>G/p.Asn47Ser in five patients, c.258G>A/p.Met86IIe in two patients, and c.115+6T>C and c.169G>A/p.Val57IIe in one patient each. All mutations were heterozygous. Comparison with the human genome database and reported literature suggested that these variants may not be pathogenic mutations causing palmoplantar pustulosis. Furthermore, there was no difference in disease severity, onset age, or disease duration between patients with these heterozygous IL36RN variants and those without (p > 0.1). Study limitation: Lack of the further evaluation of IL36Ra protein in palmoplantar pustulosis lesions. Conclusions: The four variants of IL36RN identified did not appear to be associated with the specific phenotypes of palmoplantar pustulosis.

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Psoríase/genética , Interleucinas/genética , Mutação , Fenótipo , Psoríase/patologia , China , Análise de Sequência de DNA , Estatísticas não Paramétricas , Grupo com Ancestrais do Continente Asiático/genética , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Estudos de Associação Genética , Dermatoses do Pé/genética , Dermatoses do Pé/patologia , Dermatoses da Mão/genética , Dermatoses da Mão/patologia , Heterozigoto
J. bras. nefrol ; 41(3): 393-399, July-Sept. 2019. graf
Artigo em Inglês | LILACS (Américas) | ID: biblio-1040251


Abstract Lipoprotein glomerulopathy (LPG) is an uncommon cause of nephrotic syndrome and/or kidney failure. At microscopy, LPG is characterized by the presence of lipoprotein thrombi in dilated glomerular capillaries due to different ApoE mutations. ApoE gene is located on chromosome 19q13.2, and can be identified in almost all serum lipoproteins. ApoE works as a protective factor in atherosclerosis due its interaction with receptor-mediated lipoprotein clearance and cholesterol receptor. Most common polymorphisms include ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3, and ApoE4/4. All age-groups can be affected by LPG, with a discrete male predominance. Compromised patients typically reveal dyslipidemia, type III hyperlipoproteinemia, and proteinuria. LPG treatment includes fenofibrate, antilipidemic drugs, steroids, LDL aphaeresis, plasma exchange, antiplatelet drugs, anticoagulants, urokinase, and renal transplantation. Recurrence in kidney graft suggests a pathogenic component(s) of extraglomerular humoral complex resulting from abnormal lipoprotein metabolism and presumably associated to ApoE.

Resumo A glomerulopatia por lipoproteínas (GLP) é uma patologia rara que causa síndrome nefrótica e/ou insuficiência renal. Na microscopia, a GLP é caracterizada pela presença de trombos de lipoproteínas em capilares glomerulares dilatados devido a diferentes mutações no gene da ApoE. O gene da ApoE está localizado no cromossomo 19q13.2 e pode ser identificado em quase todas as lipoproteínas séricas. A ApoE age como fator de proteção na arterioesclerose por conta de sua interação com a depuração de lipoproteínas mediada por receptores e com o receptor de colesterol. Dentre os polimorfismos mais comuns destacam-se ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3 e ApoE4/4. A GLP pode acometer indivíduos de todas as faixas etárias, com discreta predominância do sexo masculino. Pacientes afetados tipicamente apresentam dislipidemia, hiperlipoproteinemia tipo III e proteinúria. O tratamento da GLP é conduzido com fenofibrato, antilipêmicos, corticosteroides, LDL-aferese, troca de plasma, antiplaquetários, anticoagulantes, uroquinase e transplante renal. Recidiva no enxerto renal indica a existência de componentes patogênicos do complexo humoral extraglomerular resultante de metabolismo lipoproteico anômalo, possivelmente associado a ApoE.

Humanos , Masculino , Feminino , Pré-Escolar , Adulto , Pessoa de Meia-Idade , Nefropatias/patologia , Nefropatias/terapia , Apolipoproteínas E/genética , Fatores Sexuais , Transplante de Rim , Resultado do Tratamento , Nefropatias/complicações , Nefropatias/genética , Falência Renal Crônica/cirurgia , Falência Renal Crônica/etiologia , Mutação , Hipolipemiantes/uso terapêutico