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1.
Arch. argent. pediatr ; 118(1): 52-56, 2020-02-00. tab, ilus
Artigo em Inglês, Espanhol | LILACS (Américas), BINACIS | ID: biblio-1095588

RESUMO

El amplio espectro de aberraciones cromosómicas observable en los trastornos del neurodesarrollo no siempre puede ser caracterizado por análisis cromosómico. El objetivo del trabajo fue determinar la etiología genética de estos trastornos en pacientes con afecciones neurológicas congénitas y sospecha clínica de un síndrome genético, aplicando un algoritmo de estudio clínico-molecular. En 71 de 111 niños analizados, se hallaron aberraciones submicroscópicas asociadas a síndromes de microdeleción-microduplicación: DiGeorge (22 casos), Prader-Willi (26 casos), Angelman (2 casos), Williams-Beuren (17 casos), Smith-Magenis (1 caso), Miller-Dieker (1 caso) y síndrome cri du chat (1 caso). Adicionalmente, se detectó una inserción desbalanceada de novo de la región 17p12p11.2, en el punto 5p13.1, en un niño de tres años. La utilización del método clínico unido a técnicas moleculares, como hibridación fluorescente in situ, ha permitido, en la mayoría de los casos, el diagnóstico certero de pacientes y/o familias con trastornos del neurodesarrollo.


The wide range of chromosome aberrations seen in neurodevelopmental disorders may not always be characterized by means of a chromosome analysis. The objective of this study was to determine the genetic etiology of these disorders in patients with congenital neurological conditions and clinical suspicion of a genetic disorder using a clinical and molecular testing algorithm. Among 111 studied children, 71 showed submicroscopic chromosome aberrations associated with microdeletion/microduplication syndromes: DiGeorge (22 cases), Prader-Willi (26 cases), Angelman (2 cases), Williams-Beuren (17 cases), Smith-Magenis (1 case), Miller-Dieker (1 case), and cri du chat syndrome (1 case). Additionally, a de novo trisomy 17p12p11.2 due to an unbalanced insertion into 5p13.1 was identified in a 3-year-old child. In most cases, the use of a clinical method together with molecular techniques, such as fluorescence in situ hybridization, has allowed to make an accurate diagnosis in patients and/or families with neurodevelopmental disorders.


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Transtornos do Neurodesenvolvimento/diagnóstico , Doenças Genéticas Inatas/diagnóstico , Síndrome , Algoritmos , Deficiências do Desenvolvimento , Estudos Retrospectivos , Hibridização in Situ Fluorescente , Procedimentos Clínicos , Transtornos do Neurodesenvolvimento/etiologia , Aconselhamento Genético
2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781306

RESUMO

OBJECTIVE@#To explore the genetic basis for a fetus with Dandy-Walker malformation.@*METHODS@#G-banding chromosomal karotyping, single nucleotide polymorphism microarray (SNP array) and fluorescence in situ hybridization (FISH) were carried out for the fetus. Chromosomal karyotyping and FISH assay were also carried out for both parents.@*RESULTS@#SNP array has detected a 4266 kb microdeletion at 6p25.3p25.1 in the fetus, which was confirmed by FISH. FISH analysis of the parents demonstrated that the father has carried a cryptic t(6;14) (p25.1;p13) translocation, while the fetus has a der(6)t(6;14)(p25.1;p13) derived the paternal translocation.@*CONCLUSION@#The der(6)t(6;14)(p25.1;p13) probably underlies the Dandy-Walker malformation in the fetus. The 6p25.3p25.1 microdeletion is due to unbalanced gametes produced by the father's cryptic balanced translocation.


Assuntos
Síndrome de Dandy-Walker , Diagnóstico , Genética , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Gravidez , Diagnóstico Pré-Natal , Translocação Genética
3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781296

RESUMO

OBJECTIVE@#To carry out multipath cytogenetic analysis of a rare case of acute myeloid leukemia (AML) with 11q23 aberration and D13S319 deletion.@*METHODS@#G+R banding technique was used to analyze the chromosomal karyotype of the patient after 24 h of cell culture. Combined interphase and metaphase fluorescence in situ hybridization (FISH) was used to detect specific chromosomal sites for complex translocations and minor missing fragments.@*RESULTS@#The patient was found to harbor MLL-AF10 fusion gene due to rearrangement of the mixed lineage leukemia (MLL) gene in conjunct with deletion of the D13S319 locus on chromosome 13.@*CONCLUSION@#Whether MLL gene rearrangement and absence of D13S319 locus has a double impact on AML should attract more attention. For AML patient with clonal abnormalities such as 13q-, del(13)(q14), -13 or der(13), FISH assay should be proof and considered to determine the size of missing fragment so as targeted therapy may be implemented.


Assuntos
Células Cultivadas , Cromossomos Humanos Par 11 , Genética , Humanos , Hibridização in Situ Fluorescente , Interfase , Cariotipagem , Leucemia Mieloide Aguda , Genética , Metáfase , Translocação Genética
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781295

RESUMO

OBJECTIVE@#To delineate the clinical features,inheritance pattern, and genotype-phenotype correlation of a Chinese patient with a 17q25.3 duplication.@*METHODS@#Whole exome sequencing(WES), chromosomal microarray analysis (CMA), chromosomal karyotyping and fluorescence in situ hybridization (FISH) were employed for the analysis of the proband and his family members.@*RESULTS@#A 5.7 Mb duplication at 17q25.3→qter was identified by WES and CMA in the 4-year-old boy with multiple congenital anomalies, which was classified as a clinically pathogenic variant. This duplication was confirmed by FISH, and was inherited from his unaffected mother who carried a balanced translocation. Further study revealed that his grandmother also carried the balanced translocation but had gestated three healthy children and had no abortion history. His uncle also carried the balanced translocation, while his aunt was normal.@*CONCLUSION@#Above results have enriched the clinical phenotypes of 17q25.3 duplication. Genetic counseling was provided for the family. P4HB, ACTG1, BAIAP2 and TBCD genes may underlie the clinical features for the 17q25.3 duplication.


Assuntos
Anormalidades Múltiplas , Genética , Adulto , Pré-Escolar , China , Duplicação Cromossômica , Cromossomos Humanos Par 17 , Genética , Deficiências do Desenvolvimento , Genética , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Proteínas Associadas aos Microtúbulos , Translocação Genética
5.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-811193

RESUMO

Breast adenomyoepitheliomas are composed of a biphasic proliferation of myoepithelial cells around small epithelial-lined spaces. Due to the rarity of adenomyoepitheliomas, the molecular data describing them are limited. Adenomyoepitheliomas are considered to be benign or have low malignant potential, and be prone to local recurrence. Malignant transformation has been associated with homozygous deletion of CDKN2A or somatic mutations in TERT, but remains unexplained in many cases. Here, we describe a case of carcinomatous transformation of both epithelial and myoepithelial cells in an estrogen receptor-negative adenomyoepithelioma caused by amplification of MYC. Break-apart fluorescence in situ hybridization revealed an increase in the MYC gene copy number (3–4 copies/cell in 37%, > 4 copies/cell in 40%). Deregulation of MYC is responsible for uncontrolled proliferation and cellular immortalization in basal-like breast cancers. Our case demonstrates that genomic instability events associated with gene amplification may be involved in the carcinogenesis of malignant adenomyoepitheliomas.


Assuntos
Adenomioepitelioma , Neoplasias da Mama , Mama , Carcinogênese , Estrogênios , Fluorescência , Amplificação de Genes , Genes myc , Instabilidade Genômica , Hibridização In Situ , Hibridização in Situ Fluorescente , Recidiva
6.
Rev. MED ; 27(1): 45-52, ene.-jun. 2019. graf
Artigo em Espanhol | LILACS (Américas) | ID: biblio-1115218

RESUMO

Resumen: El trastorno del desarrollo sexual (TDS) testicular XX es una patología que se presenta en un individuo con cariotipo 46,XX con un fenotipo anatómico de genitales externos masculinos, que pueden variar desde la normalidad hasta la ambigüedad genital. Clínicamente se han descrito dos subgrupos de hombres 46,XX con SRY-negativos y SRY-positivos, dependiendo de la presencia o no del gen SRY que normalmente se encuentra en el cromosoma Y participando en la determinación testicular. En este artículo se describen los antecedentes personales y los hallazgos clínicos de un infante con anomalías del meato urinario en el cual se identificó un complemento cromosómico 46,XX. También, se realizó hibridación in situ fluorescente en linfocitos de sangre periférica que demostró la ausencia del gen SRY y confirmó la presencia de dos cromosomas X.


Abstract XX testicular disorder of sex development (DSD) is a pathology that occurs in an individual with a 46,XX karyotype and an anatomical phenotype of male external genitalia, which may vary from normal to ambiguous. Clinically, two subgroups of SRY-negative and SRY-positive, 46, XX men have been described, depending on the presence of the SRY gene that is normally found on the Y chromosome participating in testicular determination. This article describes the personal history and clinical findings of an infant with urethral meatus abnormalities in whom a 46,XX chromosome set was identified. Also, fluorescent in situ hybridization was performed in peripheral blood lymphocytes which demonstrated the absence of the SRY gene and confirmed the presence of two X chromosomes.


Resumo: O transtorno do desenvolvimento sexual (TDS) testicular XX é uma patologia apresentada em um indivíduo com cariótipo 46,XX com um fenótipo anatômico de genitais externos masculinos, que podem variar da normalidade à ambiguidade genital. Clinicamente, são descritos dois subgrupos de homens 46,XX com SRY-negativos e SRY-positivos, dependendo da presença ou não do gene SRY que normalmente se encontra em Y cromossomo participando da determinação testicular. Neste artigo, são descritos os antecedentes pessoais e os achados clínicos de uma criança com anomalias de meato urinário em que foi identificado um complemento cromossômico 46,XX. Além disso, foi rea -lizada hibridação in situ fluorescente em linfócitos de sangue periférico que demonstrou a ausência do gene SRY e confirmou a presença de dois cromossomos X.


Assuntos
Humanos , Masculino , Pré-Escolar , Transtornos 46, XX do Desenvolvimento Sexual , Hibridização in Situ Fluorescente , Genes sry , Transtornos Ovotesticulares do Desenvolvimento Sexual
7.
Rev. Hosp. Niños B.Aires ; 61(272): 9-17, abr. 2019.
Artigo em Espanhol | LILACS (Américas) | ID: biblio-995556

RESUMO

El SD22q11.2 está asociado a síndromes de DiGeorge, velocardiofacial, facioconotruncal y Cayler, reconocidos con la misma etiología: microdeleción 22q11.2. El fenotipo es variable y presenta cardiopatía conotruncal (CC), dismorfias faciales, anomalías palatinas, inmunodeficiencias y trastornos del neurodesarrollo. Las manifestaciones endocrinológicas que predominan son talla baja, hipocalcemia neonatal asociada a hipoparatiroidismo y disfunción tiroidea. El 90% de los afectados presenta una deleción típica de 3-Mb, mientras que el resto tiene deleciones de menor tamaño o deleción localizada más distal a la región crítica . El objetivo del trabajo es identificar en una cohorte de 63 pacientes con sospecha clínica de SD22q11.2, la presencia de la microdeleción 22q11.2 empleando como método diagnóstico la técnica de FISH y describir brevemente las características clínicas más prevalentes que presentan los pacientes con resultado de FISH positivo y negativo. La microdeleción 22q11.2 se identificó en el 38% (24/63) de los pacientes estudiados. Las características clínicas más prevalentes en este grupo fueron las cardiopatías congénitas conotruncales (95,6%), microcefalia (50%), inmunodeficiencias (50%), hipocalcemia (48,8%), anomalías del paladar (45,8%), retraso del desarrollo y déficit cognitivo (41,5%). En nuestro hospital, el algoritmo diagnóstico para la detección de la microdeleción 22q11.2 es el cariotipo de alta resolución y el estudio por la técnica de FISH.


DS22q11.2 is associated with a wide spectrum of clinical disorders (DiGeorge, velocardiofacial, facioconotrunal and Cayler syndromes) known to arise from the same etiology 22q11.2 microdeletion The phenotype is variable and includes conotruncal cardiac defect (CCD), facial phenotype, palate anomalies, inmunodeficiency and developmental disorders. The endocrine manifestations are short stature (ST), neonatal hypocalcemia due to hypoparathyroidism, and thyroid dysfunction. In 90% of patients with 22q11.1 deletion a common 3-Mb deletion has been found, whereas the rest of cases share a smaller deletion or more distal atypical deletions. The aim of the present study was to identify the 22q11.2 microdeletion by FISH in 63 patients from the Genetic and Endocrinology Division between 2002 and 2017 who had more than one clinical feature of DS22q11. 2. High resolution karyotype and fluorescent in situ hybridization (FISH) were performed with different commercial probes. The 22q11.2 microdeletion was demonstrated in 24/63 patients (38%). The more relevant clinical features in this group were: conotruncal cardiac defect (95.6%), microcephaly (50%), immunodeficiency (50%), hypocalcaemia (48.8%) palate anomalies (45.8%), development delay and cognitive deficit (41.5%). In our hospital, the diagnostic algorithm for the detection of the 22q11.2 microdeletion is the high resolution karyotype and the study by the FISH technique.


Assuntos
Humanos , Hibridização in Situ Fluorescente , Síndrome de DiGeorge , Síndrome da Deleção 22q11 , Endocrinologia , Genética
8.
Rev. colomb. cancerol ; 23(1): 3-11, ene.-mar. 2019. tab, graf
Artigo em Espanhol | LILACS (Américas) | ID: biblio-1042743

RESUMO

Resumen Introducción: La hibridación in situ fluorescente (FISH) es una herramienta fundamental en oncopatología para confirmar el diagnóstico de algunas patologías, al igual que determinar el pronóstico y el tratamiento. Objetivo: Describir la experiencia del Instituto Nacional de Cancerología de Colombia (INC) con la técnica de FISH en las diferentes neoplasias hematológicas y tumores sólidos para conocer el comportamiento molecular de nuestra población. Materiales y métodos: Se realizó un estudio descriptivo retrospectivo de todos los resultados de FISH que se han realizado en tumores hematológicos y tumores sólidos en el laboratorio de Genética y Oncología Molecular del INC, entre 2012 y 2016. Resultados: En total se realizaron 1.713 pruebas de FISH, 1.010 (59%) fueron desarrolladas en neoplasias de origen hematolinfoide y 703 (41%) en tumores sólidos, de estos 428 (61%) correspondieron para HER2 de cáncer de seno. En tumores de tejidos blandos fueron evaluadas las sondas MDM2/CDK4, EWSR1, SS18, FUS, CHOP observando positividad en el 10%, el 43%, el 44%, el 20% y el 63%, respectivamente. En cáncer de pulmón se observó positividad en el 12%. Además se realizó estudios para la detección de melanoma y para la detección la codeleción del 1p/19q en gliomas. Discusión: En el INC de Colombia se confirmó la utilidad de la técnica de FISH como complemento en el diagnóstico, el pronóstico y el factor predictivo en el manejo de pacientes con cáncer. Observamos que la prevalencia de algunas pruebas varían de la reportadas en la literatura médica (C-MYC para linfomas, ALK para cáncer de pulmón).


Abstract Introduction: Fluorescent in situ hybridization (FISH) is a fundamental tool in oncopathology to confirm the diagnosis of some pathologies, as well as to determine the prognosis and treatment. Keywords: FISH; Hybridization; Lymphomas; Leukemia; Sarcomas; HER2 Objective: To describe the experience of the FISH in the National Institute of Cancerology of Colombia (INC) in different hematological malignancies and solid tumors to know the molecular behavior of our population. Materials and methods: A retrospective descriptive study was conducted of all the FISH results that have been carried out in the Genetics and Molecular Oncology laboratory of the INC between 2012 and 2016 in hematological tumors and solid tumors. Results: A total of 1713 FISH tests were performed, 1010 (59%) were developed in neoplasms of hematolymphoid origin and 703 (41%) in solid tumors, of these 428 (61%) corresponded to breast cancer (HER2). In soft tissue tumors, MDM2 / CDK4, EWSR1, SS18, FUS, CHOP probes were evaluated, observing positivity in 10%, 43%, 44%, 20% and 63%, respectively. In lung cancer, it has observed positivity in 12%. In addition, studies have been carried out to detect melanoma and to detect the 1p / 19q deletions in gliomas. Discussion: The INC of Colombia confirms the usefulness of the FISH technique as a complement in the diagnosis, prognosis and predictive factor in the management of patients with cancer. We observed that the prevalence of some tests varies from that reported in the medical literature (C-MYC for lymphomas, ALK for lung cancer).


Assuntos
Humanos , Terapêutica , Hibridização in Situ Fluorescente , Sarcoma , Leucemia , Genes erbB-2 , Neoplasias Hematológicas , Linfoma
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-819035

RESUMO

OBJECTIVE@#To conduct genetic analysis in a fetus with complex translocation of four chromosomes.@*METHODS@#G-banded chromosome karyotype analysis, single nucleotide polymorphism array (SNP array) and fluorescence hybridization (FISH) were performed in a fetus with multiple malformations. Peripheral blood chromosome karyotype and FISH were also carried out for the parents.@*RESULTS@#The fetal amniotic fluid karyotype was 46, XY, t(12; 13)(q22; q32). SNP array analysis showed that there were 20 192 kb duplication at 1q42.13q44 and 13 293 kb deletion at 15q26.1q26.3 in the fetus. The results of karyotype and SNP array were inconsistent. FISH analyses on the parental peripheral blood samples demonstrated that the mother was a cryptic 46, XX, t(1; 15)(q42.1; q26.1) translocation. The fetus had inherited 46, XY, t(12; 13)(q22; q32) from his father and der(15)t(1; 15)(q42.1; q26.1) from his mother.@*CONCLUSIONS@#The 1q42.13q44 duplication and 15q26.1q26.3 deletion may have contributed to the abnormal sonographic features of the fetus. The combination of cytogenetic, SNP array and FISH techniques was beneficial for providing an accurate genetic counseling.


Assuntos
Aberrações Cromossômicas , Feminino , Feto , Anormalidades Congênitas , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Polimorfismo de Nucleotídeo Único , Translocação Genética
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772031

RESUMO

OBJECTIVE@#To delineate laboratory and clinical characteristics of a case with chronic myelogenous leukemia (CML) and co-occurrence of t(9;22)(q34;q11) and t(8;21)(q22;q22).@*METHODS@#The patient was subjected to cytogenetic, molecular, morphological and immunophenotypic analyses.@*RESULTS@#Cytogenetic analysis revealed presence of t(8;21)(q22;q22) in addition to t(9;22)(q34;q11) in the patient. Chimeric BCR/ABL and AML1/ETO genes were detected by fluorescence in situ hybridization (FISH). Transcripts of BCR/ABL210 and AML1/ETO fusion genes were detected by relative quantity PCR. Morphological study suggested that the patient was at the chronic phase of CML. No significant immunophenotypic abnormality was detected by flow cytometry.@*CONCLUSION@#Co-occurrence of t(8;21)(q22;q22) and t(9;22)(q34;q11) is rare in CML. Only 5 similar cases have been described previously. This case suggested that chromosomal alterations may precede morphological, flow cytometric and clinical changes and accelerate progression of the disease.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos , Proteínas de Fusão bcr-abl , Humanos , Hibridização in Situ Fluorescente , Leucemia Mielogênica Crônica BCR-ABL Positiva , Genética , Translocação Genética
12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772029

RESUMO

OBJECTIVE@#To explore the prenatal screening and diagnosis for a pair of monochorionic-diamniotic (MCDA) twins discordant for 45,X/46,XX mosaicism.@*METHODS@#Amniotic fluid samples were taken from both twins for whom non-invasive prenatal testing has signaled a high risk for sex chromosomal abnormality. Uncultured amniotic fluid was analyzed by fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array). Conventional G-banded karyotyping analysis was performed on the cultured amniotic fluid.@*RESULTS@#Metaphase chromosome analysis showed that one of the twins had a mos 45,X[11]/46,XX[26] karyotype, while the other had a normal karyotype. FISH and SNP-array applied on uncultured amniotic fluid revealed about 30% mosaicism in one of the twins. The twins were confirmed to be monozygotic by SNP-array analysis.@*CONCLUSION@#To avoid confusion arising from discordant karyotypes in MCDA twins with abnormal non-invasive prenatal testing (NIPT) results, dual amniocentesis should be carried out to obtain amniotic fluid samples for chromosomal as well as molecular analysis. To determine the ratio of 45,X and 46,XX cells in Turner syndrome can provide valuable information for prenatal genetic counseling.


Assuntos
Amniocentese , Cromossomos Humanos X , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Mosaicismo , Gravidez , Diagnóstico Pré-Natal
13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772028

RESUMO

OBJECTIVE@#To explore the genetic basis of a fetus with ventricular septal defect (VSD) by using modified noninvasive prenatal testing (NIPT) for the detection of microdeletion syndromes.@*METHODS@#Chromosomal karyotypes of the fetus and its parents were analyzed by G-banding technique. Next generation sequencing (NGS) was used to detect genomic copy number variations (CNVs) in cell-free fetal DNA. The results were verified by fluorescence in situ hybridization (FISH).@*RESULTS@#The fetus and its parents all had a normal karyotype at 320-400 band level. NGS revealed a deletion of 1.30 Mb at 7q11.23 in the fetus, with a 93% overlap with that of Williams-Beuren syndrome (WBS). The father also had a deletion of 1.42 Mb at 7q11.23, with a 99% overlap with that of WBS. Modified NIPT also detected the 1.30 Mb deletion at 7q11.23 in the fetus. The result of FISH has confirmed the above results.@*CONCLUSION@#It is necessary to carry out genetic testing on fetuses with VSD. NGS can detect fetal microdeletion syndromes and help to trace their parental origin. The modified NIPT for fetal chromosomal microdeletions/microduplication syndromes is highly accurate.


Assuntos
Variações do Número de Cópias de DNA , Feminino , Testes Genéticos , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Gravidez , Diagnóstico Pré-Natal , Síndrome de Williams
14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772016

RESUMO

OBJECTIVE@#To analyze the clinical and molecular biological characteristics of a neonate with myeloid proliferation related to Down syndrome (DS).@*METHODS@#The neonate, who was suspected for Down syndrome, was analyzed in terms of clinical feature, peripheral blood cell morphology, fluorescence in situ hybridization (FISH), immunological classification and other laboratory tests. On hundred and fourteen leukemia-related genes were subjected to next-generation sequencing (NGS).@*RESULTS@#Laboratory test revealed obvious abnormal liver function and coagulation function, anemia, and extreme leukocytosis. Cell smear indicated significantly increased progenitor cells, which conformed to proliferation of megakaryocytes. FISH showed trisomy 21. By NGS, c.220+dupT, a novel mutation, was identified in exon 2 of the GATA1 gene, which encodes a N-terminal activation domain and has a frequency of 95.8%. No mutation was identified among the remaining 113 genes.@*CONCLUSION@#The neonate had DS and GATA1 gene mutation. High percentage of circulating blasts should be considered as transient myelodysplasia but not congenital leukemia.


Assuntos
Síndrome de Down , Genética , Fator de Transcrição GATA1 , Genética , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Mutação , Trissomia
15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772015

RESUMO

OBJECTIVE@#To explore the mechanism and duration of false positive results of non-invasive prenatal testing (NIPT) caused by vanishing twins.@*METHODS@#To detect the variation of cell-free fetal DNA fraction before and after the fetal death and explore its influence on the results of NIPT at different gestational weeks. Prenatal diagnosis was also carried out on amniotic fluid sample derived from the survivor twin. After birth, the two placentas and papyraceous fetus were obtained to ascertain the definitive genetic diagnosis and pathological changes through fluorescence in situ hybridization, fluorescence quantitative PCR and histopathological examination. Eight cases of vanishing twins leading to discordant NIPT results were reviewed for determining the duration of this influence.@*RESULTS@#The vanishing twin has led to immediate flooding of cfDNA into the maternal plasma due to necrotic cytotrophoblasts, which in turn caused increased release of fetal DNA in a short time. However, this did not change the NIPT result for a period of time. The tissue and chorionic villi of perished fetus presented extensive degenerative necrosis.@*CONCLUSION@#The false positive NIPT result caused by vanishing twins may be attributed to continuous release of DNA fragments into the maternal plasma by the fetuses. The influence of the vanished fetuses, which may lead to discordant NIPT results, can last for at least 7-8 weeks but no more than 12-14 weeks during the first and second trimester.


Assuntos
DNA , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente , Gravidez , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal
16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771997

RESUMO

OBJECTIVE@#To study the correlation of hematomorphology, bone marrow cytogenetics and clinical biochemical parameters with the prognosis of non-Hodgkin's lymphoma with bone marrow invasion.@*METHODS@#Morphological analysis of bone marrow cells was performed by routine bone marrow puncture.Chromosome samples were prepared by short-term bone marrow culture. Karyotype analysis was carried out by R-banding in 28 patients. P53 gene was detected by fluorescence in situ hybridization (FISH). Serum lactate dehydrogenase (LDH) of all patients was determined and compared.@*RESULTS@#In all patients, bone marrow morphology showed invasion of lymphoma. Chromosome analysis revealed abnormal karyotypes in 19 cases, which yielded an incidence of 67.85%. The proportion of lymphoma cells in bone marrow among those with an abnormal karyotype was much higher than those with a normal karyotype (60.2% vs. 33.5%, P<0.05). FISH assay showed that 9 (32.14%) patients had P53 gene deletion. And the deletion was much more common among those with an abnormal karyotype (42.11% vs. 11.11%, P<0.05). The serum LDH level in patients with an abnormal karyotype was significantly higher compared with whose with a normal karyotype (1464.37 U/L vs. 294.33 U/L, P<0.05).@*CONCLUSION@#Patients with abnormal karyotypes have a higher rate of P53 gene deletion, and their LDH level is significantly higher than those with a normal karyotype, which predicted a relatively poor prognosis.


Assuntos
Adulto , Medula Óssea , Criança , Aberrações Cromossômicas , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Linfoma não Hodgkin
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771984

RESUMO

OBJECTIVE@#To explore the genetic cause for a patient with intellectual disability, short stature and multiple congenital anomalies, and to correlate the result with the clinical phenotype.@*METHODS@#Routine karyotyping analysis was carried out on GTG-banded metaphase chromosomes. Single nucleotide polymorphism (SNP) microarray was used to detect microdeletions or microduplications in the patient. Fluorescence in situ hybridization (FISH) was used to ascertain the origin of aberrant chromosomes.@*RESULTS@#The karyotype of the patient was 46,XY,der(18), while both of his parents had a normal karyotype. SNP array identified a 1.23 Mb deletion at 18p11.32-pter (chr18: 136 227-1 370 501, hg19) and a 33.76 Mb duplication at 18q21.1-qter (chr18: 44 250 359-78 013 728, hg19) in the patient. Above finding was confirmed by dual-color FISH with one color for 18p and another for 18q. The patient presented with some common features of 18p deletion and 18q duplication including intellectual disability and growth retardation, in addition with some features of 18p deletion including pectus excavatum, short stature and growth hormone (GH) deficiency. The patient showed progressive improvement of stature with GH therapy. Comparison of patients with previously reported dup(18q)+del(18p) recombinations suggested that, even for patients with similar breakpoints, their phenotypes have ranged from normal to severe and there were no consistent findings.@*CONCLUSION@#As aberrations involving double chromosomal segments often result in phenotypic variability, it has been difficult to correlate the genotype of our patient with his phenotype.


Assuntos
Anormalidades Múltiplas , Deleção Cromossômica , Cromossomos Humanos Par 18 , Genótipo , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Monossomia , Fenótipo , Trissomia
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771980

RESUMO

OBJECTIVE@#To determine the origin of supernumerary small marker chromosomes (sSMCs) carried by two fetuses.@*METHODS@#Single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) analysis were carried out on cells cultured from the amniotic fluid samples.@*RESULTS@#SNP-array analysis showed both fetuses to be arr[hg19]22q11.1q11.21(16 888 899-18 649 190)×4, with a duplicated 1.7 Mb region (16 888 899-18 649 190) leading to partial tetrasomy of 22q11.1-22q11.21. FISH confirmed that both fetuses were 47,XN,+mar.ish idic(22)(q11.2) (RP11-958H20 ++),which suggested a diagnosis of Cat-eye syndrome (CES). The appearance of abortuses were consistent with the diagnosis of CES.@*CONCLUSION@#Two fetuses with CES were diagnosed by genetic testing. The latter has provided a basis for genetic counseling.


Assuntos
Aneuploidia , Transtornos Cromossômicos , Diagnóstico , Cromossomos Humanos Par 22 , Anormalidades do Olho , Diagnóstico , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Gravidez , Diagnóstico Pré-Natal
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771973

RESUMO

OBJECTIVE@#To explore the genetic basis for a fetus featuring growth restriction and validate the effectiveness of a novel noninvasive prenatal testing (NIPT) technique for the detection of chromosomal microdeletions.@*METHODS@#Next-generation sequencing(NGS) and fluorescence in situ hybridization(FISH) were used to analyze the DNA of the fetus. Conventional G-banding was used to analyze the karyotypes of the fetus and its parents. High-throughput sequencing was used to analyze free fetal DNA.@*RESULTS@#NGS analysis has revealed a 4.88 Mb deletion at 15q11.2-q13.1 region in the fetus, which has a 99% overlap with the critical region of Prader-Willi syndrome (Type 2) and Angelman syndrome (Type 2) and encompassed critical genes including SNRPN and UBE3A. NIPT also revealed a 4.6 Mb deletion at 15q12, which was consistent with the results of fetal cord blood and amniotic DNA testing. FISH assay has confirmed the result of NGS. By karyotying, all subjects showed a normal karyotypes at a level of 320~400 bands.@*CONCLUSION@#It is quite necessary to carry out genetic testing on fetuses showing growth restriction. NIPT for fetal chromosomal microdeletions/microduplication syndromes is highly accurate for the diagnosis of Prader-Willi/Angelman syndrome.


Assuntos
Síndrome de Angelman , Bandeamento Cromossômico , Cromossomos Humanos Par 15 , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente , Síndrome de Prader-Willi , Gravidez
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771970

RESUMO

OBJECTIVE@#To characterize the molecular genetics of 81 patients with acute monocytic leukemia (AML).@*METHODS@#Fluorescence in situ hybridization (FISH) was employed to detect MLL gene rearrangements. Combined mutations of 17 genes were detected by DNA-based PCR and Sanger sequencing.@*RESULTS@#Sixty seven patients were found to harbor at least one mutation. The most commonly mutated gene was NPM1 (n=18), which was followed by FLT3-ITD (n=16), NRAS (n=16), DNMT3A (n=15), TET2 (n=12), RUNX1 (n=11) and KRAS (n=9). Based on the functions of mutated genes, the most frequently involved genes were those involved in DNA methylation (38.27%), tyrosine kinase receptor signaling (32.1%), transcription regulation (28.4%), and RAS pathway (24.7%). Single gene mutation predominated in patient with cytogenetic abnormalities, while coexistence of 2 mutations have predominated in patient with normal cytogenetic findings. Stratified by cytogenetic findings, patients with single gene mutations (intermediate-risk group) had significantly higher complete remission (CR) rates than those with ≥2 gene mutations (unfavorable-risk group) (91.7% vs. 57.6% , 87.5% vs. 25.0%, P =0.0319, 0.0117, respectively).@*CONCLUSION@#Over 80% of AML patients were found to harbor at least one mutation. Their clinical phenotype and prognosis may be impacted by the synergy of MLL gene rearrangement and multiple mutations. For patients under the same risk stratification, the number of mutations is reversely correlated with the CR rate.


Assuntos
Citogenética , Humanos , Hibridização in Situ Fluorescente , Leucemia Monocítica Aguda , Leucemia Mieloide Aguda , Mutação , Prognóstico , Tirosina Quinase 3 Semelhante a fms
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