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1.
Front Immunol ; 9: 2397, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30386343

RESUMO

LRBA deficiency was first described in 2012 as an autosomal recessive disorder caused by biallelic mutations in the LRBA gene (OMIM #614700). It was initially characterized as producing early-onset hypogammaglobulinemia, autoimmune manifestations, susceptibility to inflammatory bowel disease, and recurrent infection. However, further reports expanded this phenotype (including patients without hypogammaglobulinemia) and described LRBA deficiency as a clinically variable syndrome with a wide spectrum of clinical manifestations. We present the case of a female patient who presented with type 1 diabetes, psoriasis, oral thrush, and enlarged liver and spleen at the age of 8 months. She later experienced recurrent bacterial and viral infections, including pneumococcal meningitis and Epstein Barr viremia. She underwent two consecutive stem cell transplants at the age of 8 and 9 years, and ultimately died. Samples from the patient and her parents were subjected to whole exome sequencing, which revealed a homozygous 1-bp insertion in exon 23 of the patient's LRBA gene, resulting in frameshift and premature stop codon. The patient's healthy mother was heterozygous for the mutation and her father tested wild-type. This finding suggested that either one copy of the paternal chromosome 4 bore a deletion including the LRBA locus, or the patient inherited two copies of the mutant maternal LRBA allele. The patient's sequencing data showed a 1-Mb loss of heterozygosity region in chromosome 4, including the LRBA gene. Comparative genomic hybridization array of the patient's and father's genomic DNA yielded normal findings, ruling out genomic copy number abnormalities. Here, we present the first case of LRBA deficiency due to a uniparental disomy (UPD). In contrast to classical Mendelian inheritance, UPD involves inheritance of 2 copies of a chromosomal region from only 1 parent. Specifically, our patient carried a small segmental isodisomy of maternal origin affecting 1 Mb of chromosome 4.

2.
PLoS One ; 13(10): e0205692, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30332465

RESUMO

In families at risk from monogenic diseases affected offspring, it is fundamental the development of a suitable Double Factor Preimplantation Genetic Testing (DF-PGT) method for both single-gene analysis and chromosome complement screening. Aneuploidy is not only a major issue in advanced-maternal-age patients and balanced translocation carriers, but also the aneuploidy rate is extremely high in patients undergoing in vitro fertilization (IVF), even in young donors. To adequate NGS technology to the DF-PGT strategy four different whole genome amplification systems (Sureplex, MALBAC, and two multiple displacement amplification systems-MDA) were tested using TruSight One panel on cell lines and blastocyst trophectoderm biopsies-TE. Embryo cytogenetic status was analyzed by Nexus software. Sureplex and MALBAC DNA products were considered not suitable for PGT diagnosis due to inconsistent and poor results on Trusight one (TSO) panel. Results obtained with both MDA based methods (GEH-MDA and RG-MDA) were appropriate for direct mutation detection by TSO NGS platform. Nevertheless, RG-MDA amplification products showed better coverage and lower ADO rates than GEH-MDA. The present work also demonstrates that the same TSO sequencing data is suitable not only for the direct mutation detection, but also for the indirect mutation detection by linkage analysis of informative SNPs. The present work also demonstrates that Nexus software is competent for the detection of CNV by using with TSO sequencing data from RG-MDA products, allowing for the whole cytogenetic characterization of the embryos. In conclusion, successfully development of an innovative and promising DF-PGT strategy using TSO-NGS technology in TE biopsies, performed in-house in a single laboratory experience, has been done in the present work. Additional studies should be performed before it could be used as a diagnostic alternative in order to validate this approach for the detection of chromosomal aneuploidies.

3.
An. pediatr. (2003. Ed. impr.) ; 89(1): 3-11, jul. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-176977

RESUMO

Fundamento y objetivo: La citogenética convencional detecta un 3-5% de los pacientes con retraso global del desarrollo/discapacidad intelectual y/o malformaciones congénitas. La amplificación de sondas múltiples dependientes de ligación permite incrementar la tasa diagnóstica entre 2,4-5,8%. Actualmente, los arrays de hibridación genómica comparada o aCGH son la herramienta diagnóstica con mayor rendimiento en estos pacientes, en malformaciones congénitas y trastornos del espectro autista. El objetivo del presente trabajo ha sido evaluar la eficiencia del uso del aCGH como técnica de primera línea diagnóstica en estas y otras indicaciones (epilepsia, talla baja). Pacientes y método: Se ha estudiado a 1.000 pacientes afectados por las patologías mencionadas mediante la técnica de aCGH. Resultados: Se detectaron desequilibrios de efecto patogénico en un 14% de los pacientes (140/1.000). Según el fenotipo, se diagnosticaron un 18,9% de los pacientes afectados de retraso global del desarrollo/discapacidad intelectual; un 13,7% de las malformaciones congénitas; un 9,76% de las patologías psiquiátricas, un 7,02% de los casos con epilepsia y un 13,3% de los pacientes con talla baja. Dentro de las malformaciones congénitas destacan las del sistema nervioso central con un 14,9% y las cardiopatías congénitas con un 10,6% de diagnósticos. En las patologías psiquiátricas destacan los pacientes con trastornos del espectro autista, con un 8,9% de diagnósticos. Conclusiones: Nuestros resultados demuestran la efectividad y la eficiencia de la utilización del aCGH como test de primera línea en el diagnóstico genético de los pacientes con sospecha de desequilibrios genómicos. Todo ello avala su inclusión dentro del Sistema Nacional de Salud


Background and objective: Conventional cytogenetics diagnoses 3-5% of patients with unexplained developmental delay/intellectual disability and/or multiple congenital anomalies. The Multiplex Ligation-dependent Probe Amplification increases diagnostic rates from between 2.4 to 5.8%. Currently the comparative genomic hybridisation array or aCGH is the highest performing diagnostic tool in patients with developmental delay/intellectual disability, congenital anomalies and autism spectrum disorders. Our aim is to evaluate the efficiency of the use of aCGH as first-line test in these and other indications (epilepsy, short stature). Patients and method: A total of 1000 patients referred due to one or more of the abovementioned disorders were analysed by aCGH. Results: Pathogenic genomic imbalances were detected in 14% of the cases, with a variable distribution of diagnosis according to the phenotypes: 18.9% of patients with developmental delay/intellectual disability; 13.7% of multiple congenital anomalies, 9.76% of psychiatric pathologies, 7.02% of patients with epilepsy, and 13.3% of patients with short stature. Within the multiple congenital anomalies, central nervous system abnormalities and congenital heart diseases accounted for 14.9% and 10.6% of diagnoses, respectively. Among the psychiatric disorders, patients with autism spectrum disorders accounted for 8.9% of the diagnoses. Conclusions: Our results demonstrate the effectiveness and efficiency of the use of aCGH as the first line test in genetic diagnosis of patients suspected of genomic imbalances, supporting its inclusion within the National Health System


Assuntos
Humanos , Criança , Hibridização Genômica Comparativa/economia , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/economia , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/economia , Análise Custo-Benefício , Deficiência Intelectual/genética , Deficiências do Desenvolvimento/genética
4.
Clin Immunol ; 191: 44-51, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29572183

RESUMO

There is scarce literature about autoinflammation in syndromic patients. We describe a patient who, in addition to psychomotor and growth delay, presented with fevers, neutrophilic dermatosis, and recurrent orogenital ulcers. Comparative Genomic Hybridization (CGH) array permitted to identify a 13.13Mb deletion on chromosome 6, encompassing 53 genes, and including TNFAIP3 gene (A20). A20 is a potent inhibitor of the NF-kB signalling pathway and restricts inflammation via its deubiquitinase activity. Western blotting and immunoprecipitation assays showed decreased A20 expression and increased phosphorylation of p65 and IkBa. Patient's cells displayed increased levels of total K63-linked ubiquitin and increased levels of ubiquitinated RIP and NEMO after stimulation with TNF. We describe the molecular characterization of an autoinflammatory disease due to a large chromosomal deletion and review the phenotypes of patients with A20 haploinsufficiency. CGH arrays should be the first diagnostic method for comprehensive analysis of patients with syndromic features and immune dysregulation.

5.
Eur J Med Genet ; 61(5): 269-272, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29307792

RESUMO

The transcription factor SOX18 has been shown to play a role in the development of hair, blood and lymphatic vessels. Mutations in SOX18 result in hereditary lymphedema, with the unique clinical association of hypotrichosis and telangiectasia (HLTS). Some patients present with additional disease features which may be explained by the location of SOX18 mutation. We report a patient with hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) confirmed by detection of a novel mutation in the SOX18 gene. Few cases of HTLS have been reported in the literature. We reviewed all cases reported to date to delineate the clinical manifestations that allow us to prompt diagnosis of this syndrome for appropriate management and genetic counseling.


Assuntos
Hipotricose/genética , Linfedema/genética , Fatores de Transcrição SOXF/genética , Telangiectasia/genética , Pré-Escolar , Humanos , Hipotricose/patologia , Linfedema/patologia , Masculino , Mutação , Síndrome , Telangiectasia/patologia
6.
An Pediatr (Barc) ; 89(1): 3-11, 2018 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-28958749

RESUMO

BACKGROUND AND OBJECTIVE: Conventional cytogenetics diagnoses 3-5% of patients with unexplained developmental delay/intellectual disability and/or multiple congenital anomalies. The Multiplex Ligation-dependent Probe Amplification increases diagnostic rates from between 2.4 to 5.8%. Currently the comparative genomic hybridisation array or aCGH is the highest performing diagnostic tool in patients with developmental delay/intellectual disability, congenital anomalies and autism spectrum disorders. Our aim is to evaluate the efficiency of the use of aCGH as first-line test in these and other indications (epilepsy, short stature). PATIENTS AND METHOD: A total of 1000 patients referred due to one or more of the abovementioned disorders were analysed by aCGH. RESULTS: Pathogenic genomic imbalances were detected in 14% of the cases, with a variable distribution of diagnosis according to the phenotypes: 18.9% of patients with developmental delay/intellectual disability; 13.7% of multiple congenital anomalies, 9.76% of psychiatric pathologies, 7.02% of patients with epilepsy, and 13.3% of patients with short stature. Within the multiple congenital anomalies, central nervous system abnormalities and congenital heart diseases accounted for 14.9% and 10.6% of diagnoses, respectively. Among the psychiatric disorders, patients with autism spectrum disorders accounted for 8.9% of the diagnoses. CONCLUSIONS: Our results demonstrate the effectiveness and efficiency of the use of aCGH as the first line test in genetic diagnosis of patients suspected of genomic imbalances, supporting its inclusion within the National Health System.

8.
Cytogenet Genome Res ; 146(3): 181-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26382598

RESUMO

Copy number variants (CNVs) of the Williams-Beuren syndrome (WBS) 7q11.23 region are responsible for neurodevelopmental disorders with multisystem involvement and variable expressivity. We found 2 patients with a deletion and 1 patient with a duplication in this region sharing a common breakpoint located between the LIMK1 and EIF4H(WBSCR1) genes. One patient had a WBS phenotype, although testing with a commercially available FISH assay was negative for the deletion. A further test using array CGH showed an atypical WBS region deletion. The second patient showed global developmental delay, speech delay and poor motor skills with a deletion outside the WBS region. The third patient had manifestations compatible with an autism spectrum disorder showing a duplication in the WBS region. Our findings point to the existence of a previously unrecognized recurrent breakpoint responsible for rearrangements in the WBS region. Given that most commercial FISH assays include probes flanking this novel breakpoint, further testing with array CGH should be performed in patients with WBS and negative FISH results.


Assuntos
Sítios Frágeis do Cromossomo , Síndrome de Williams/genética , Pré-Escolar , Hibridização Genômica Comparativa , Feminino , Humanos , Masculino
9.
Eur J Hum Genet ; 23(12): 1615-26, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25853300

RESUMO

Array comparative genomic hybridization (aCGH) is a powerful genetic tool that has enabled the identification of novel imbalances in individuals with intellectual disability (ID), autistic disorders and congenital malformations. Here we report a 'genotype first' approach using aCGH on 13 unrelated patients with 19p13.3 submicroscopic rearrangement (11 deletions and 2 duplications) and review cases in the literature and in public databases. Shared phenotypic features suggest that these patients represent an interstitial microdeletion/microduplication syndrome at 19p13.3. Common features consist of abnormal head circumference in most patients (macrocephaly with the deletions and microcephaly with the duplications), ID with developmental delay (DD), hypotonia, speech delay and common dysmorphic features. The phenotype is associated with at least a ~0.113 Mb critical region harboring three strong candidate genes probably associated with DD, ID, speech delay and other dysmorphic features: MAP2K2, ZBTB7A and PIAS4, an E3 ubiquitin ligase involved in the ubiquitin signaling pathways, which we hypothesize for the first time to be associated with head size in humans.


Assuntos
Deleção Cromossômica , Duplicação Cromossômica , Cromossomos Humanos Par 19/genética , Deficiências do Desenvolvimento/genética , Megalencefalia/genética , Microcefalia/genética , Proteínas Inibidoras de STAT Ativados/genética , Criança , Pré-Escolar , Proteínas de Ligação a DNA/genética , Deficiências do Desenvolvimento/patologia , Feminino , Humanos , Lactente , MAP Quinase Quinase 2/genética , Masculino , Megalencefalia/patologia , Microcefalia/patologia , Proteínas de Ligação a Poli-ADP-Ribose , Síndrome , Fatores de Transcrição/genética
11.
Cytogenet Genome Res ; 147(4): 209-11, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26974471

RESUMO

Small supernumerary marker chromosomes (sSMC) originating from chromosome 10 are rare and usually found in mosaic form. We present a de novo apparently non-mosaic sSMC(10) prenatally diagnosed in amniotic fluid and postnatally confirmed in peripheral blood. Characterization by array-CGH showed a pericentromeric duplication of 7.1 Mb of chromosome 10. The fetus did not show ultrasound abnormalities, and a normal female phenotype was observed during a 3-year postnatal follow-up. The absence of phenotypic abnormalities in the present case provides evidence of a non-critical pericentromeric region in 10p11.21q11.1 (hg19 35,355,570-42,448,569) associated with a duplication.


Assuntos
Duplicação Cromossômica , Cromossomos Humanos Par 10 , Adulto , Pré-Escolar , Hibridização Genômica Comparativa , Feminino , Seguimentos , Humanos , Cariotipagem , Gravidez , Diagnóstico Pré-Natal
12.
Cytogenet Genome Res ; 144(4): 290-3, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25720458

RESUMO

Very few cases of constitutional interstitial deletions of the proximal short arm of chromosome 3 have been reported; however, the proximal 3p deletion is emerging as a clinically recognizable syndrome. We present an intrachromosomal insertion of 3p12.3p14.1 in a phenotypic normal man (46,XY,ins(3)(p25p12.3p14.1)) which is responsible for the unbalanced karyotype in 2 affected offspring, one with a 3p12.3p14.1 interstitial deletion and the other with a reciprocal duplication. The exceptionality of these 2 reciprocal recombinants contributes to a better definition of the proximal 3p deletion syndrome and its duplication counterpart.


Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 3/genética , Criança , Pré-Escolar , Duplicação Cromossômica , Feminino , Humanos , Hibridização in Situ Fluorescente , Mutagênese Insercional , Deleção de Sequência , Irmãos
13.
Diagn. prenat. (Internet) ; 24(3): 117-125, jul.-sept. 2013.
Artigo em Espanhol | IBECS | ID: ibc-115219

RESUMO

Introducción. Se conocen numerosas reestructuraciones cromosómicas compatibles con un fenotipo normal, principalmente algunos cromosomas marcadores sin contenido genéticamente relevante y heteromorfismos cromosómicos. Material y métodos. Estudio retrospectivo de 20.098 casos prenatales. Resultados. Se han detectado 24/17.784 casos (0,13%) de pequeños cromosomas marcadores (SMC) en líquido amniótico, 8/2.223 (0,36%) en vellosidad corial y 31/20.007 (0,15%) reestructuraciones estructurales clasificadas como heteromorfismos. Conclusiones. Se proponen guías de actuación basándose en nuestra experiencia y la bibliografía existente(AU)


Introduction. Many chromosome reorganizations compatible with a normal phenotype are known, mainly some marker chromosomes with no genetically relevant content or chromosomal heteromorphisms. Material and methods. Retrospective study of 20,098 prenatal cases. Results. We detected 24/17,784 cases (0.13%) of small marker chromosomes (SMCs) in amniotic fluid, 8/2223 (0.36%) in chorionic villus, and 31/20,007 (0.15%) structural reorganizations classified as heteromorphisms. Conclusions. Clinical practice guidelines are proposed based on our experience and the literature(AU)


Assuntos
Humanos , Masculino , Feminino , Diagnóstico Pré-Natal/instrumentação , Diagnóstico Pré-Natal/métodos , Fenótipo , Marcadores Genéticos/genética , Marcadores Genéticos/fisiologia , Diagnóstico Pré-Natal/normas , Diagnóstico Pré-Natal/tendências , Diagnóstico Pré-Natal , Somatotipos/genética , Marcadores Genéticos , Marcadores Genéticos/imunologia , Mapeamento Cromossômico/instrumentação , Mapeamento Cromossômico , Estudos Retrospectivos
14.
Am J Med Genet A ; 161A(9): 2363-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23894094

RESUMO

We present a clinical and molecular cytogenetic characterization of two new patients with a complex supernumerary marker consisting of the entire short arm of chromosome 18 with a chromosome 13/21 centromere. One patient is a girl with a nonsyndromic intellectual disability and the second is a prenatally diagnosed fetus. To our knowledge, these are the fourth and fifth such cases to be described in the literature, suggesting the existence of a possible recurring constitutional structural chromosome abnormality.


Assuntos
Centrômero , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 21 , Trissomia/genética , Adolescente , Adulto , Aberrações Cromossômicas , Bandeamento Cromossômico , Cromossomos Humanos Par 18/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Hibridização in Situ Fluorescente , Gravidez , Diagnóstico Pré-Natal , Trissomia/diagnóstico
15.
Gene ; 524(2): 381-5, 2013 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-23639959

RESUMO

Xq28 duplication, including the MECP2 gene, is among the most frequently identified Xq subtelomeric rearrangements. The resulting clinical phenotype is named Lubs syndrome and mainly consists of intellectual disability, congenital hypotonia, absent speech, recurrent infections, and seizures. Here we report a Mexican male patient carrying a supernumerary marker chromosome with de novo Xq28 gain. By MLPA, duplication of MECP2, GDI1, and SLC6A8 was found and a subsequent a-CGH analysis demonstrated that the gain spanned ~2.1Mb. Despite gain of the MECP2 gene, the features of this patient do not evoke Lubs syndrome. Probably the mosaicism of the supernumerary marker chromosome is modifying the phenotype in this patient.


Assuntos
Síndrome de Resistência a Andrógenos/genética , Duplicação Cromossômica/genética , Anormalidades Craniofaciais/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Deficiência Intelectual/genética , Proteína 2 de Ligação a Metil-CpG/genética , Transtornos dos Cromossomos Sexuais/genética , Adolescente , Síndrome de Resistência a Andrógenos/patologia , Facies , Proteína do X Frágil de Retardo Mental/genética , Marcadores Genéticos , Variação Genética , Humanos , Lactente , Masculino , México , Reação em Cadeia da Polimerase Multiplex , Proteínas do Tecido Nervoso/genética , Fenótipo , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/genética
17.
Hum Genet ; 131(3): 513-23, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21975797

RESUMO

Novel methodologies for detection of chromosomal abnormalities have been made available in the recent years but their clinical utility in prenatal settings is still unknown. We have conducted a comparative study of currently available methodologies for detection of chromosomal abnormalities after invasive prenatal sampling.A multicentric collection of a 1-year series of fetal samples with indication for prenatal invasive sampling was simultaneously evaluated using three screening methodologies: (1) karyotype and quantitative fluorescent polymerase chain reaction (QF-PCR), (2) two panels of multiplex ligation-dependent probe amplification (MLPA), and (3) chromosomal microarray-based analysis (CMA) with a targeted BAC microarray. A total of 900 pregnant women provided informed consent to participate (94% acceptance rate). Technical performance was excellent for karyotype, QF-PCR, and CMA (~1% failure rate), but relatively poor for MLPA (10% failure). Mean turn-around time (TAT) was 7 days for CMA or MLPA, 25 for karyotype, and two for QF-PCR, with similar combined costs for the different approaches. A total of 57 clinically significant chromosomal aberrations were found (6.3%), with CMA yielding the highest detection rate (32% above other methods). The identification of variants of uncertain clinical significance by CMA (17, 1.9%) tripled that of karyotype and MLPA, but most alterations could be classified as likely benign after proving they all were inherited. High acceptability, significantly higher detection rate and lower TAT, could justify the higher cost of CMA and favor targeted CMA as the best method for detection of chromosomal abnormalities in at-risk pregnancies after invasive prenatal sampling.


Assuntos
Transtornos Cromossômicos/genética , Análise de Sequência com Séries de Oligonucleotídeos , Diagnóstico Pré-Natal/métodos , Adulto , Aberrações Cromossômicas , Feminino , Humanos , Cariótipo , Análise de Sequência com Séries de Oligonucleotídeos/economia , Gravidez , Diagnóstico Pré-Natal/economia , Sensibilidade e Especificidade
18.
Diagn. prenat. (Internet) ; 22(3): 86-91, jul.-sept. 2011. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-108624

RESUMO

El diagnóstico prenatal citogenético durante el primer trimestre de gestación se realiza a partir de biopsias de vellosidad corial. Para la obtención de metafases se utilizan dos métodos: el cultivo corto o semidirecto (STC) y cultivo largo (LTC). La principal ventaja del STC es que no presenta contaminación materna y la del LTC es que no hay descritos en la literatura falsos negativos. Se considera que la combinación de las dos técnicas (STC y LTC) es la estrategia diagnóstica más eficaz para este tipo de estudios. La técnica de PCR cuantitativa fluorescente (QF-PCR) permite evaluar las aneuploidías más frecuentemente implicadas en el diagnóstico prenatal en 24-48 horas en muestras de vellosidad corial. El objetivo de este trabajo es evaluar la combinación de QF-PCR y LTC como sustituto de las clásicas STC y LTC para el diagnóstico prenatal en muestras de vellosidad corial. Para ello presentamos nuestra experiencia en 900 muestras de vellosidad corial(AU)


First trimester cytogenetic prenatal diagnosis is performed on chorionic villus biopsies. Two methods are used to obtain metaphases: the short-term or semi-direct culture (STC) and long term culture (LTC). The main advantage of STC is that there is no risk of maternal contamination, and of LTC that no false-negative findings are described in the literature. It is considered that the combination of the two techniques (STC and LTC) is the most effective diagnostic strategy for this type of study. The technique of quantitative fluorescent PCR (QF-PCR) allows the evaluation of aneuploidy most frequently involved in prenatal diagnosis in 24-48 hours in chorionic villus samples. The aim of this study is to evaluate the combination of QF-PCR and LTC as a substitute for classical STC and LTC for prenatal diagnosis in chorionic villus samples. We present our experience in 900 chorionic villus samples(AU)


Assuntos
Humanos , Masculino , Feminino , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal , Reação em Cadeia da Polimerase/instrumentação , Reação em Cadeia da Polimerase/métodos , Citogenética/métodos , Análise Citogenética/métodos , Análise Citogenética/estatística & dados numéricos , Análise Citogenética , Amostra da Vilosidade Coriônica/instrumentação , Amostra da Vilosidade Coriônica/métodos , Diagnóstico Pré-Natal/tendências , Reação em Cadeia da Polimerase/normas , Citogenética/organização & administração , Reação em Cadeia da Polimerase , Diagnóstico Pré-Natal/instrumentação , Citogenética/normas , Amostra da Vilosidade Coriônica/normas , Amostra da Vilosidade Coriônica
19.
J Mol Diagn ; 12(6): 828-34, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20889556

RESUMO

Quantitative fluorescent PCR (QF-PCR) has been used by many laboratories for prenatal diagnosis of the most common aneuploidies. QF-PCR is rapid, cost-effective, and suitable for automation and can detect most abnormalities diagnosed by conventional karyotyping. Whether QF-PCR should be used alone in most of the samples and in which karyotyping should also be offered is currently a topic of debate. We evaluated and compared the results obtained from 7679 prenatal samples in which conventional karyotype and QF-PCR had been performed, including 1243 chorionic villi and 6436 amniotic fluid samples. Concordant QF-PCR and karyotype results were obtained in 98.75% of the samples. An abnormal karyotype associated with adverse clinical outcome undetected by QF-PCR was found in 0.05% of samples. Therefore, QF-PCR can be used alone in a large number of samples studied in a prenatal laboratory, thereby reducing both the workload in cytogenetic laboratories and parental anxiety when awaiting results.


Assuntos
Reação em Cadeia da Polimerase/métodos , Diagnóstico Pré-Natal/métodos , Líquido Amniótico/química , Vilosidades Coriônicas/química , Aberrações Cromossômicas , Feminino , Marcadores Genéticos , Humanos , Cariotipagem/métodos , Gravidez
20.
Urology ; 75(2): 347-55, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19647297

RESUMO

OBJECTIVES: To classify bladder tumors according to their genomic imbalances and evaluate their association with patient's outcome. METHODS: Sixty-three superficially and minimally invasive bladder tumors were analyzed by conventional comparative genomic hybridization. Subtelomeric screening in 15 of these tumors was performed by multiplex ligation-dependent probe amplification. RESULTS: Losses of 9q and 9p (32% and 25% of all cases, respectively) as well as gains of chromosomes Xq and Xp (28% and 25%, respectively) were the most frequent chromosome imbalances. Losses of 8p and gains in 1q and 8q were detected in >20% of cases. Tumors were classified into 3 groups according to their individualized pattern of gains and losses. The largest group was characterized by few chromosome imbalances, presenting 77% and 49% of the Ta and T1 tumors, respectively. Another group characterized by chromosomal gains, was composed of equal number of Ta and T1 tumors, with +1q and +17q gains being the most common imbalances. A minority group was characterized by chromosomal losses on 11q, 5q, and 6q. The multiplex ligation-dependent probe amplification study showed good correlation with comparative genomic hybridization results. With regard to the biological significance of this classification, a remarkable fact is that this minority group composed mainly of T1 tumors, showed a significant decrease in patient overall survival. CONCLUSIONS: Our data suggest that superficial carcinomas of the bladder can be subdivided into a larger number of subclasses than had previously been expected. Our results also demonstrate a decreased survival among patients whose tumors show more genomic losses than gains.


Assuntos
Hibridização Genômica Comparativa , Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/patologia
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