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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(2): 150-152, 2020 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-32034742

RESUMO

OBJECTIVE: To identify pathological mutation of D4Z4 in a child with facioscapulohumeral muscular dystrophy (FSHD) presented initially as mental retardation. METHODS: Wechsler Intelligence Scale for Children Revised in China (WISC-IV) was used to assess the patient's IQ. Other clinical data was also collected. With genomic DNA extracted from peripheral blood samples, the child and his parents were subjected to medical exome sequencing and copy number variation analysis by next generation sequencing (NGS). The D4Z4 repeats and their origin source were determined by molecular combing. RESULTS: By the WISC-IV test, the child was found to have a total IQ of 41, with a speech comprehension IQ of 45, and perceptual inference index IQ of 52. No pathological mutation was detected by NGS. By molecular combing method, the child was found to carry a D4Z4 spanning 5.2 kb with a copy number of 2. Analysis of his parents indicate that the mutation was de novo. CONCLUSION: The D4Z4 copy number variation may account for the FSHD and mental retardation in the child. The molecular combing method can be used to identify the number of repeat units and facilitate the diagnosis of FSHD.


Assuntos
Deficiência Intelectual , Distrofia Muscular Facioescapuloumeral , Criança , China , Cromossomos Humanos Par 4 , Variações do Número de Cópias de DNA , Humanos , Deficiência Intelectual/genética , Distrofia Muscular Facioescapuloumeral/genética , Mutação
2.
Int J Cancer ; 146(5): 1219-1229, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31087647

RESUMO

We previously identified a novel breast cancer susceptibility variant on chromosome 4q31.22 locus (rs1429142) conferring risk among women of European ancestry. Here, we report replication of findings, validation of the variant in diverse populations and fine-mapping of the associated locus in Caucasian population. The SNP rs1429142 (C/T, minor allele frequency 18%) showed association for the overall breast cancer risk in Stages 1-4 (n = 4,331 cases/4271 controls; p = 4.35 × 10-8 ; odds ratio, ORC-allele ,1.25), and an elevated risk among premenopausal women (n = 1,503 cases/4271 controls; p = 5.81 × 10-10 ; ORC-allele 1.40) in European populations. SNP rs1429142 was associated with premenopausal breast cancer risk in women of African (T/C; p-value 1.45 × 10-02 ; ORC-allele 1.2) but not from Chinese ancestry. Fine-mapping of the locus revealed several potential causal variants which are present within a single association signal, revealed from the conditional regression analysis. Functional annotation of the potential causal variants revealed three putative SNPs rs1366691, rs1429139 and rs7667633 with active enhancer functions inferred based on histone marks, DNase hypersensitive sites in breast cell line data. These putative variants were bound by transcription factors (C-FOS, STAT1/3 and POL2/3) with known roles in inflammatory pathways. Furthermore, Hi-C data revealed several short-range interactions in the fine-mapped locus harboring the putative variants. The fine mapped locus was predicted to be within a single topologically associated domain, potentially facilitating enhancer-promoter interactions possibly leading to the regulation of nearby genes.


Assuntos
Neoplasias da Mama/genética , Cromossomos Humanos Par 4/genética , Loci Gênicos/genética , Predisposição Genética para Doença , Pré-Menopausa , Adulto , Grupo com Ancestrais do Continente Africano/genética , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Alberta/epidemiologia , Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Mapeamento Cromossômico , Conjuntos de Dados como Assunto , Elementos Facilitadores Genéticos/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Pós-Menopausa , Regiões Promotoras Genéticas/genética , Adulto Jovem
3.
Adv Exp Med Biol ; 1185: 197-202, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884611

RESUMO

Current application of next-generation sequencing (NGS) leads to detection of the underlying disease-causing gene and mutation or mutations in from 60% to 85% of patients with inherited retinal diseases (IRDs), depending on the methods used, disease type, and population tested. In a cohort of 320 families with autosomal dominant retinitis pigmentosa (adRP), we have detected the mutation in 82% of cases using a variety of methods, leaving more than 50 families with "elusive" disease genotypes. All of the remaining families have been screened for mutations in known IRD genes using retinal-targeted-capture NGS, and most have been tested by whole-exome NGS. Linkage mapping has been conducted in several large families. In one of these families, with DNA samples from ten affected family members and six unaffected, linking members, we observed substantial maximum two-point LOD scores for linkage to both chromosomes 2 and 4. Subsequent 10X Genomics Chromium™ sequencing, which facilitates linked-read, phase-known chromosomal analysis, revealed a balanced translocation of the q terminus arms of chromosomes 2 and 4 involving 35 Mb and 73 Mb of 2 and 4, respectively. The balanced translocation is present in all affected family members and absent from all unaffected individuals. Family histories suggest multiple miscarriages are associated with the translocation. The breakpoint on chromosome 4 is within or 5' to the LRAT gene, whereas the chromosome 2 break is in a gene-poor region. We conclude that the balanced translocation is the cause of adRP in this family, which may lead to dysregulation of the LRAT gene. Since multiple miscarriages are a hallmark of balanced translocations, this possibility should be considered in evaluating family histories. Further, large structural variants, which are not easily detected by conventional sequencing methods, may account for a significant fraction of the remaining unsolved families.


Assuntos
Retinite Pigmentosa/genética , Translocação Genética , Aciltransferases/genética , Cromossomos Humanos Par 2 , Cromossomos Humanos Par 4 , Análise Mutacional de DNA , Proteínas do Olho , Genes Dominantes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Linhagem , Retina/patologia
4.
Medicine (Baltimore) ; 98(50): e18268, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852098

RESUMO

RATIONALE: Wolf-Hirschhorn Syndrome (WHS) is a rare disorder caused by the loss of the distal part of the short arm of chromosome 4, and has various phenotypes depending on the deletion size. Although many articles report on urinary tract malformations or ophthalmologic abnormalities, there are few descriptions of the skeletal anomalies. This is an extremely rare case of cervical dysplasia in WHS. PATIENT CONCERNS: A 24-year-old pregnant woman was transferred to our hospital at 21 gestational weeks for intrauterine growth retardation and oligohydramnios and decided to preserve the pregnancy after evaluation. A female was born at full term by normal vaginal delivery, weighing 1791 g. The patient was suspected to have congenital dysplasia of the cervical vertebrae on the routine newborn chest radiograph, and cervical spine magnetic resonance imaging revealed nonossification of the C3 and C4 vertebral bodies. DIAGNOSIS: The newborn had the "Greek warrior helmet" face typical of WHS. A deletion was detected in the distal portion of the short arm of chromosome 4 (p 16.3) by fluorescence in situ hybridization analysis. INTERVENTIONS: She was hospitalized for nutritional management and congenital anomaly evaluation for a month before being discharged with rehabilitation and antiepileptic drugs. OUTCOMES: The patient has been readmitted with seizure attacks 5 times to date. At one year of age, she still shows severe head lag and feeding problems. Her last weight was below the 3rd centile. LESSONS: Although cervical dysplasia is a rarely reported morphology in WHS, it may provide artefacts for diagnosing WHS as cervical anomalies, unlike facial anomalies or developmental delays, are seldom found in congenital disease.


Assuntos
Doenças do Desenvolvimento Ósseo/etiologia , Vértebras Cervicais/patologia , Cromossomos Humanos Par 4/genética , Síndrome de Wolf-Hirschhorn/complicações , Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/genética , Deleção Cromossômica , Feminino , Humanos , Recém-Nascido , Cariotipagem , Imagem por Ressonância Magnética , Fenótipo , Gravidez , Síndrome de Wolf-Hirschhorn/diagnóstico , Síndrome de Wolf-Hirschhorn/genética , Adulto Jovem
5.
Cytogenet Genome Res ; 159(3): 130-136, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31715598

RESUMO

We report on a female patient who presented with severe intellectual disability and autistic behavior, dysmorphic features, orodental anomalies, and bilateral calcification of basal ganglia. Using a high-density oligonucleotide microarray, we have identified a de novo duplication of 11q13.1q22.1 involving the dosage sensitive genes FGF3 and FGF4, genes related to autosomal dominant disorders KMT5B, GAL, SPTBN2, and LRP5, susceptibility loci SCZD2, SLEH1, and SHANK2, mitochondrial genes NDUFV1, NDUFS8, and TMEM126B, and many loss of function genes, including PHOX2A, CLPB, MED17, B3GNT1, LIPT2, and CLPB. However, the duplication did not involve Ribonuclease H2, subunit C (RNASEH2C) which is considered to be located in the critical region for Aicardi-Goutières syndrome. In combination with the duplication at 11q13.1, a 1.849-Mb heterozygous duplication at 4q35.2 was also identified. Although this duplicated region does not contain causative genes related to brain calcification, the duplication at 4q35 was reported previously in a patient with basal ganglia calcification, coats' like retinopathy, and glomerulosclerosis. Our patient's presentation and genomic findings indicate that duplication of 4q35.2 could be a novel genetic cause of calcification of basal ganglia. Our report also underscores the clinical significance of rearrangements in 11q13.1q22.1 in the pathogenesis of basal ganglia calcification.


Assuntos
Gânglios da Base/patologia , Calcinose/genética , Duplicação Cromossômica , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 4 , Fenótipo , Criança , Bandeamento Cromossômico , Feminino , Humanos , Cariotipagem
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 989-992, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598942

RESUMO

OBJECTIVE: To explore the nature and origin of chromosomal copy number variants (CNVs) in a pedigree affected with mental retardation. METHODS: Genomic CNVs of the proband were analyzed by next generation sequencing (NGS). Chromosomal karyotypes of the proband and his relatives were analyzed with high-resolution karyotyping and fluorescence in situ hybridization (FISH). RESULTS: Clinical phenotypes of the proband and other patients from the pedigree included mental retardation and mild dysmorphism. The results of NGS revealed that the proband carried a 16.24 Mb microduplication at 4p16.3-15.32 and a 2.2 Mb microdeletion at 8p23.3-23.2. Other patients of the pedigree harbored the same variants, while those without the phenotypes did not harbor the variants. The results of high-resolution karyotyping and FISH revealed that the mother of the proband carried a reciprocal translocation between 4p and 8p, and her karyotype was 46,XX,t(4;8)(p16;p23). No karyotypic abnormality was detected in his father. CONCLUSION: The abnormal phenotypes of this pedigree may be attributed to 4p microduplication in conjunct with 8p microdeletion derived from a maternal balanced translocation between 4p and 8p.


Assuntos
Aberrações Cromossômicas , Duplicação Cromossômica , Testes Genéticos , Deficiência Intelectual/genética , Cromossomos Humanos Par 4 , Cromossomos Humanos Par 8 , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Linhagem , Fenótipo
7.
BMC Med Genet ; 20(1): 134, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382906

RESUMO

BACKGROUND: Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome caused by partial 4p deletion highly variable in size in individual patients. The core WHS phenotype is defined by the association of growth delay, typical facial characteristics, intellectual disability and seizures. The WHS critical region (WHSCR) has been narrowed down and NSD2 falls within this 200 kb region. Only four patients with NSD2 variants have been documented with phenotypic features in detail. CASE PRESENTATION: Herein, we report the case of a 12-year-old boy with developmental delay. He had dysmorphic facial features including wide-spaced eyes, prominent nasal bridge continuing to forehead, abnormal teething and micrognathia. He also had mild clinodactyly of both hands. Using whole-exome sequencing, we identified a pathogenic mutation in NSD2 [c.4029_4030insAA, p.Glu1344Lysfs*49] isolated from peripheral blood DNA. Sanger confirmation of this variant revealed it as a de novo truncating variant in the family. CONCLUSION: Here, we reported a boy with de novo truncating variant in NSD2 with atypical clinical features comparing with 4p16.3 deletion related WHS. Our finding further supported the pathogenesis of truncating variants in NSD2 and delineated the possible symptom spectrum caused by these variants.


Assuntos
Predisposição Genética para Doença/genética , Histona-Lisina N-Metiltransferase/genética , Fenótipo , Proteínas Repressoras/genética , Síndrome de Wolf-Hirschhorn/genética , Sequência de Bases , Criança , Cromossomos Humanos Par 4 , DNA/sangue , Deficiências do Desenvolvimento/genética , Humanos , Deficiência Intelectual/genética , Masculino , Convulsões/genética , Sequenciamento Completo do Exoma , Síndrome de Wolf-Hirschhorn/fisiopatologia
8.
Cytogenet Genome Res ; 158(2): 63-73, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31261151

RESUMO

Terminal deletion of chromosome 4 (4q deletion syndrome) is a rare genetic condition that is characterized by a broad clinical spectrum and phenotypic variability. Diagnosis of the distinct condition can be identified by conventional chromosome analysis and small deletions by novel molecular cytogenetic methods such as microarray comparative genome hybridization (aCGH). Prenatal diagnosis is challenging; to date 10 cases have been described. We report a prenatally diagnosed case of de novo 4q deletion syndrome confirmed by conventional karyotyping and FISH due to an elevated combined risk for Down syndrome and prenatal ultrasound findings. aCGH validated the diagnosis and offered exact characterization of the disorder. Cytogenetic and microarray results described a 4q32.1qter terminal deletion of the fetus. Prenatal ultrasound detected multiple nonstructural findings (micrognathia, choroid plexus cysts, echogenic fetal bowel, short femur, and cardiac axis deviation). Pregnancy was terminated at 20 weeks. In addition to the index patient, we reviewed the 10 prenatally published cases of 4q deletion syndrome in the literature and compared these with our results. We summarize the patients' characteristics and prenatal clinical findings. Alterations of maternal serum biochemical factors, an elevated combined risk for trisomies, and distinct ultrasonographic findings can often be observed in cases of prenatal 4q deletion syndrome and may facilitate the otherwise difficult prenatal diagnosis.


Assuntos
Transtornos Cromossômicos/diagnóstico , Hibridização in Situ Fluorescente/métodos , Cariotipagem/métodos , Diagnóstico Pré-Natal/métodos , Aborto Induzido , Adulto , Deleção Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 4/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Idade Materna , Fenótipo , Gravidez , Fatores de Risco
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(7): 682-685, 2019 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-31302910

RESUMO

OBJECTIVE: To make molecular diagnosis of an infant affected with severe developmental delay and multiple birth defects, assisting prenatal diagnosis for the second pregnancy. METHODS: Standard G-banded karyotyping was performed for the fetus and his parents. Single nucleotide polymorphism array (SNP array) was used to detect submicroscopic chromosomal aberration. Fluorescence in situ hybridization (FISH) was employed to determine the parental origin of the aberration. RESULTS: Both the proband and the fetus harbored a 5.4 Mb distal 4p deletion and a 6.9 Mb distal 6q duplication. FISH confirmed that the mother has carried a balanced translocation involving 4p and 6q. CONCLUSION: The unbalanced chromosomal aberration in the proband and the fetus were both derived from the mother. Both patients showed a Wolf-Hirschhorn syndrom phenotype and partial phenotype of 6q trisomy. SNP array combined with FISH are essential for the detection of cryptic chromosomal aberrations which may be missed by coventional karyotyping analysis.


Assuntos
Diagnóstico Pré-Natal , Translocação Genética , Síndrome de Wolf-Hirschhorn/genética , Cromossomos Humanos Par 4/genética , Cromossomos Humanos Par 6/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Masculino , Linhagem , Gravidez
10.
J Cutan Pathol ; 46(11): 844-851, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31161673

RESUMO

Herein, we describe a patient with immunoglobulin G (IgG)-lambda smoldering multiple myeloma with translocation t(4:14) who developed widespread ulcerative horny-like spicules, heralding rapid progression to overt myeloma requiring aggressive chemotherapy and autologous stem cell transplantation. The serum abnormal immunoglobulin in the blood was cryoglobulin, which typically precipitates in the tissues at low temperatures causing inflammation and tissue damage. Histopathological changes, observed in lesions at different evolutionary stages, evidenced columns of horny-like eosinophilic homogeneous material, immunoreactive for IgG lambda, protruding from the dilated and/or distorted follicular openings or acrosyringia and small vessel thrombotic vasculopathy and vasculitis in concert with an inflammatory neutrophilic and lymphocytic reaction. Biochemical investigations on material from a spicule and ulcero-necrotic lesion revealed cryoprecipitates containing IgG-lambda with electrophoretic characteristics identical to those of the serum dysprotein. Our findings suggest that the formation of spicules and development of ulcerative lesions are a part of the same clinical spectrum where the cold-dependent precipitation of the immunogenic dysprotein, both in the skin vessels and hair follicle infundibula, play a major pathogenetic role. Whether this highly characteristic paraneoplastic dermatosis can identify patients with high-risk cytogenetic abnormalities and be incorporated into prognostic models, applicable early on in the course of myeloma, warrants further investigation.


Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 4/genética , Mieloma Múltiplo , Neoplasias Cutâneas , Mieloma Múltiplo Latente , Translocação Genética , Autoenxertos , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Mieloma Múltiplo Latente/genética , Mieloma Múltiplo Latente/metabolismo , Mieloma Múltiplo Latente/patologia , Mieloma Múltiplo Latente/terapia , Transplante Autólogo
11.
Mol Biol (Mosk) ; 53(2): 268-273, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31099776

RESUMO

Many human genes that control human embryonic development and differentiation of human cells form chromosomal contact with rRNA gene clusters, which are involved in the epigenetic regulation of many genes. The sites of rRNA gene contact often fall on extended (up to 50 kb) regions containing a chromatin mark, H3K27ac histone, typical for superenhancers, as well as on pericentromeric and subtelomeric regions of chromosomes. We found that the DUX4 genes located in the subtelomeric region of human chromosome 4 are surrounded by regions that are often in contact with the rRNA genes. The 25 kb region of this chromosome, presented in version hg19 of the sequenced human genome, contains several copies of the DUX4 gene. The sites of rRNA gene contacts located around this region contain methylation sites as well as CTCF binding sites. It is assumed that the rRNA gene contacts are important in silencing these DUX4 gene copies.


Assuntos
DNA Ribossômico/genética , Desenvolvimento Embrionário/genética , Proteínas de Homeodomínio/genética , Família Multigênica/genética , Fator de Ligação a CCCTC/metabolismo , Cromatina/genética , Cromatina/metabolismo , Cromossomos Humanos Par 4/genética , Epigênese Genética , Histonas/química , Histonas/metabolismo , Humanos , Telômero/genética , Telômero/metabolismo
12.
Genome Res ; 29(6): 883-895, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31097473

RESUMO

Despite increasing insights in genome structure organization, the role of DNA repetitive elements, accounting for more than two thirds of the human genome, remains elusive. Facioscapulohumeral muscular dystrophy (FSHD) is associated with deletion of D4Z4 repeat array below 11 units at 4q35.2. It is known that the deletion alters chromatin structure in cis, leading to gene up-regulation. Here we show a genome-wide role of 4q-D4Z4 array in modulating gene expression via 3D nuclear contacts. We have developed an integrated strategy of 4q-D4Z4-specific 4C-seq and chromatin segmentation analyses, showing that 4q-D4Z4 3D interactome and chromatin states of interacting genes are impaired in FSHD1 condition; in particular, genes that have lost the 4q-D4Z4 interaction and with a more active chromatin state are enriched for muscle atrophy transcriptional signature. Expression level of these genes is restored by the interaction with an ectopic 4q-D4Z4 array, suggesting that the repeat directly modulates the transcription of contacted targets. Of note, the up-regulation of atrophic genes is a common feature of several FSHD1 and FSHD2 patients, indicating that we have identified a core set of deregulated genes involved in FSHD pathophysiology.


Assuntos
Cromatina/genética , Cromossomos Humanos Par 4 , Distrofia Muscular Facioescapuloumeral/genética , Sequências de Repetição em Tandem , Transcrição Genética , Biomarcadores , Células Cultivadas , Montagem e Desmontagem da Cromatina/genética , Expressão Ectópica do Gene , Epistasia Genética , Regulação da Expressão Gênica , Humanos , Modelos Biológicos , Proteínas Musculares/genética , Distrofia Muscular Facioescapuloumeral/diagnóstico , Proteínas Ligases SKP Culina F-Box/genética
13.
J Genet ; 982019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30945692

RESUMO

A parental diagnosis was performed for an unborn foetus of a healthy couple, who was due for ultrasound detection of multiple malformations and abnormal amniotic fluid karyotypes. For an accurate diagnosis, routine G-banding analysis and next generation sequencing (NGS) were carried out. Finally, conventional cytogenetic analysis suggested that the foetus had a karyotype of47,XX,+mar[52]/46,XN, meanwhile NGS also revealed a partial tetrasomy of 27.84Mb from 4q26-q31.21 (117,385,735-145,225,759), and G-banding analysis excluded the couple to have carried the 4q26-q31.21 duplication. We have identified a de novo mosaic small supernumerary marker chromosomes (sSMC) derived from 4q26-q31.21 in a foetus with hemivertebra, polydactyly, abnormal ears, and heart and ventricular septal defect.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Cromossomos Humanos Par 4/genética , Feto/patologia , Marcadores Genéticos , Diagnóstico Pré-Natal , Tetrassomia , Adulto , Análise Citogenética , Feminino , Feto/metabolismo , Humanos , Masculino , Mosaicismo , Gravidez
14.
Cancer Genomics Proteomics ; 16(3): 175-178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31018948

RESUMO

BACKGROUND/AIM: The aim of the study was to determine the genetic and molecular consequences of trisomy 4, a recurrent but rare chromosomal abnormality in acute myeloid leukemia (AML). MATERIALS AND METHODS: Interphase fluorescence in situ hybridization, reverse transcriptase-quantitative polymerase chain reaction for 28 chromosomal gene translocations/fusion genes, and targeted sequencing analyses were performed on five AMLs with trisomy 4 as the sole chromosomal anomaly. RESULTS: An NPM1 frameshift mutation was found in all leukemic bone marrows, DNMT3A, FLT3, and IDH1 mutations were found in three, KIT and NRAS mutations in two, whereas IDH2 (R140Q), RUNX1, and WT1 mutations were found in only one patient each. The three patients with a DNMT3A (R882H) mutation have died. In contrast, the two patients whose leukemic cells were without this mutation, are alive 55 and 31 months after diagnosis, respectively. CONCLUSION: The results suggest a possible association between trisomy 4 and additional mutations that may influence prognosis.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 4/genética , Leucemia Mieloide Aguda/genética , Trissomia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
J Cutan Pathol ; 46(8): 599-602, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30989672

RESUMO

Capicua transcriptional repressor (CIC)-rearranged sarcomas are part of the group of Ewing-like sarcomas or atypical Ewing sarcomas which, thanks to the progress in molecular diagnosis, are being defined by particular genetic abnormalities separating this group into distinct entities with their own particular histological and immunohistochemical features, as well as different survival outcomes. We report the case of a healthy 28-year-old female presenting with a tender lesion on her forearm which after ultrasound examination was clinically favored to represent an infected sebaceous cyst. Hematoxylin-eosin staining showed a lobulated neoplasm within the subcutis composed of poorly differentiated epithelioid to round cells with a small amount of amphophilic cytoplasm. Frequent mitotic figures and tumor necrosis were present. Immunohistochemical studies showed patchy focal CD99 membranous positivity, negative WT1 and TLE1 staining and diffuse nuclear positivity for ETV4 (performed at outside laboratory). FISH analysis showed significant CIC rearrangement enabling a final diagnosis of an undifferentiated small round cell sarcoma harboring the t(4;19)(q35;q13.1) and CIC-DUX4 fusion. This case shows the importance of awareness of this entity as, unlike Ewing sarcoma, these lesions present in the soft tissues rather than bone and may, as in this case, arise in the superficial soft tissues and be submitted to a dermatopathology practice.


Assuntos
Cisto Epidérmico , Antebraço , Rearranjo Gênico , Proteínas de Homeodomínio , Proteínas de Fusão Oncogênica , Proteínas Repressoras , Sarcoma de Células Pequenas , Neoplasias Cutâneas , Adulto , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 19/metabolismo , Cromossomos Humanos Par 4/genética , Cromossomos Humanos Par 4/metabolismo , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo , Cisto Epidérmico/genética , Cisto Epidérmico/metabolismo , Cisto Epidérmico/patologia , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Hibridização in Situ Fluorescente , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Sarcoma de Células Pequenas/genética , Sarcoma de Células Pequenas/metabolismo , Sarcoma de Células Pequenas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Translocação Genética , Proteínas WT1/genética , Proteínas WT1/metabolismo
18.
Int J Hematol ; 109(5): 572-577, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30887274

RESUMO

Light-chain plasma cell myeloma (LC-PCM) is a PCM subtype in which only immunoglobulin light-chain is secreted. However, the absence of immunoglobulin heavy-chain (IGH) production in this condition has not been fully elucidated. To address this issue, we retrospectively analyzed patients at our center with LC-PCM and found a group who had only split signals of IGH gene derived from 14q32/IGH translocations by fluorescence in situ hybridization (FISH). Six patients were identified with only split signals of the IGH gene derived from 14q32/IGH translocations. Five of these patients were newly diagnosed, while one had IgG-λ PCM at presentation, which transformed to λ LC-PCM after treatment. The translocation partners were identified in four patients: two cases of (11;14)(q13;q32) and two cases of (4;14)(p16;q32). The development of LC-PCM appears to be explained by the application of allelic exclusion in these patients, such that 14q32/IGH translocation in one allele contributes to the pathogenesis of PCM and the subsequent loss of the other allele is responsible for the loss of IGH production. These findings suggest that a FISH pattern of IGH with "split and loss" may constitute a unique subgroup of LC-PCM.


Assuntos
Cromossomos Humanos Par 14/genética , Cadeias lambda de Imunoglobulina , Leucemia Plasmocitária/genética , Perda de Heterozigosidade , Translocação Genética , Idoso , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 4/genética , Feminino , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética
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