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1.
Braz. j. biol ; 83: e249911, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1339366

ABSTRACT

Abstract Hematological and hematopoietic cells malignancies of the genes and hematopoietic cells are associated with the genetic mutation, often at the chromosomal level. The standard cytogenetic study is widely accepted as one of the main diagnostics and prognostic determinants in patients. Therefore, the current descriptive and cross-sectional study sought to determine the cytogenetic analysis of frequent hematological malignancies in Pakistan. A total of 202 peripheral bone marrow or blood samples from patients with benign and malignant hematological malignancy were taken using a conventional G-banding technique. Among enrolled patients, the mean age was 21.5 years ± 23.4, and gender-wise distribution showed a marked predominance of the male 147 (73%) population compared to the female 55 (27%). Patients in the age group (2-10 years) had the highest frequency, 48 (24%), of hematological neoplasms, followed by age (11-20 years) with 40 (20%). Normal karyotypes (46, XX/46, XY) was found in 51% (n=103) patients. Furthermore, the frequency of complex karyotype was 30 (15%), while normal was seen in 171 (85%) patients. Pre-B Acute Lymphoblastic Leukemia (Pre-B ALL) was the most prevalent malignancy of 66 (33%), followed by Chronic Myelogenous Leukemia (CML) of 41 (20%) and Acute Lymphocytic Leukemia of 29 (14%). Translocation was the most prevalent 50 (25%), followed by hypotriploidy 14 (7%) and monosomy 8 (4%) on chromosome aberration analysis. In addition, t(9:22) translocation was found to be 20 (10%) in CML, with the majority in the age group (31-40 years). This study recommends that karyotyping should be tested frequently in hematological conditions because it may provide insight into the relative chromosomal changes associated with particular malignancies.


Resumo As neoplasias hematológicas e de células hematopoiéticas dos genes e as células hematopoiéticas estão associadas à mutação genética, geralmente em nível cromossômico. O estudo citogenético padrão é amplamente aceito como um dos principais determinantes diagnósticos e prognósticos em pacientes. Portanto, o presente estudo descritivo e transversal buscou determinar a análise citogenética de neoplasias hematológicas frequentes no Paquistão. Um total de 202 amostras de medula óssea periférica ou sangue de pacientes com malignidade hematológica benigna e maligna foi coletado usando uma técnica convencional de banda G. Entre os pacientes inscritos, a média de idade foi de 21,5 anos ± 23,4, e a distribuição por gênero mostrou uma marcada predominância da população masculina de 147 (73%) em comparação com a feminina de 55 (27%). Pacientes na faixa etária (2-10 anos) tiveram a maior frequência, 48 (24%), de neoplasias hematológicas, seguida da idade (11-20 anos) com 40 (20%). Cariótipos normais (46, XX / 46, XY) foram encontrados em 51% (n = 103) dos pacientes. Além disso, a frequência de cariótipo complexo foi de 30 (15%), enquanto normal foi observada em 171 (85%) pacientes. Leucemia linfoblástica aguda pré-B (LLA Pré-B) foi a doença maligna mais prevalente de 66 (33%), seguida por leucemia mieloide crônica (LMC) de 41 (20%) e leucemia linfocítica aguda de 29 (14%). A translocação foi o 50 mais prevalente (25%), seguido por hipotriploidia 14 (7%) e monossomia 8 (4%) na análise de aberração cromossômica. Além disso, a translocação t (9:22) encontrada foi de 20 (10%) na LMC, com a maioria na faixa etária (31-40 anos). Este estudo recomenda que o cariótipo deve ser testado com frequência em condições hematológicas porque pode fornecer informações sobre as alterações cromossômicas relativas associadas a doenças malignas específicas.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Young Adult , Chromosome Aberrations , Hematologic Neoplasms/genetics , Hematologic Neoplasms/epidemiology , Pakistan/epidemiology , Cross-Sectional Studies , Karyotyping
2.
Braz. j. biol ; 83: e240118, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1278559

ABSTRACT

Abstract For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-1 and 1.0 mg mL-1 MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-1). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-1, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA.


Resumo Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados ​​contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-1 e 1,0 mg mL-1 foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-1 de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-1, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.


Subject(s)
Humans , Animals , Zika Virus , Zika Virus Infection , Insecticides/toxicity , DNA Damage , Chromosome Aberrations , Plant Roots , Onions , Mosquito Vectors , Malathion/toxicity , Mitotic Index
3.
J. Health Biol. Sci. (Online) ; 10(1): 1-6, 01/jan./2022. tab
Article in English | LILACS | ID: biblio-1411461

ABSTRACT

Objectives: The purpose of this study was to evaluate the mutagenic potential of fluoxetine and fluoxetine-galactomannan. Methods: Chromosomal aberration test and Salmonella typhimurium/microsome mutagenicity assay. Results: The results showed that fluoxetine (250 µg/mL) can cause chromosomal breaks of treated leukocytes and increase the frequency of reversion of the tester strains of S. typhimurium / microsome assay only at the highest concentration (5 mg/mL), while fluoxetine encapsulated in galactomannan did not cause these changes (leukocytes and S. typhimuriums strains). Conclusion: In summary, fluoxetine showed a mutagenic effect detectable only at high concentrations in both eukaryotic and prokaryotic models. Furthermore, the fluoxetine/galactomannan complex, in this first moment, prevented the mutagenicity attributed to fluoxetine, emphasizing that the present encapsulation process can be an alternative in preventing these effects in vitro.


Objetivos: avaliar o potencial mutagênico da fluoxetina e da fluoxetina-galactomanana. Métodos: Teste de aberração cromossômica e ensaio de mutagenicidade de Salmonella typhimurium /microssoma. Resultados: a fluoxetina (250 µg/mL) pode causar quebras cromossômicas de leucócitos tratados e aumentar a frequência de reversão das cepas testadoras de S. typhimurium /microssoma apenas na concentração mais alta (5 mg/mL), enquanto a fluoxetina encapsulada em galactomanano não causou essas alterações (leucócitos e cepas de S. typhimurium). Conclusão: a fluoxetina mostrou um efeito mutagênico detectável apenas em altas concentrações em modelos eucarióticos e procarióticos. Além disso, o complexo fluoxetina/galactomanan, neste primeiro momento, evitou a mutagenicidade atribuída à fluoxetina, ressaltando que o presente processo de encapsulamento pode ser uma alternativa na prevenção desses efeitos in vitro.


Subject(s)
Fluoxetine , Chromosome Aberrations , Salmonella typhimurium , Chromosome Breakage , Microsomes , Mutagenicity Tests
4.
Poblac. salud mesoam ; 19(2)jun. 2022.
Article in Spanish | LILACS-Express | LILACS, SaludCR | ID: biblio-1386939

ABSTRACT

Resumen La prevalencia mundial de la discapacidad intelectual (DI) es del 3 %. Una de las causas más comunes de DI de origen genético son las aberraciones cromosómicas, las cuales resultan fácilmente detectables mediante un cariotipo. Sin embargo, muchas de estas pasan desapercibidas durante el análisis citogenético convencional debido a su tamaño. Estas pequeñas alteraciones se pueden localizar en los subtelómeros y se ha observado que, cuando es así, constituyen una razón importante de DI en pacientes que carecen de un diagnóstico de causalidad. En este estudio de tipo observacional, se utilizó la técnica MLPA con el objetivo de determinar la frecuencia de aberraciones cromosómicas submicroscópicas en los subtelómeros en una población infantil con DI de origen desconocido. Se examinaron 70 muestras de forma exitosa y se obtuvo un caso con una microduplicación en el subtelómero 17p, para una frecuencia del 1,4 %. También, se realizó el análisis citogenético en 33 muestras y se encontró un caso con una aberración cromosómica detectable al microscopio, para una frecuencia del 3 %. El porcentaje de aberraciones cromosómicas subteloméricas fue menor al esperado en comparación con estudios similares. Finalmente, se concluyó que el cariotipo y la técnica MLPA se complementan para el abordaje de personas con DI de origen desconocido.


Abstract The prevalence of intellectual disability (ID) in the global population is 3%. One of the most frequent cause of ID are chromosome aberrations, which are easily detected by a karyotype. However, many of these maygoundetected during a conventional cytogenetic analysis because of their length.These small alterations can be localized in the subtelomeres and it has been observed that when localized there, they are an important cause of ID in patients without a causality diagnostic. In this observational study, we use the MLPA technique for the purpose of identifying the frequency of submicroscopicsubtelomere chromosomal aberrations in a population of people with ID of unknown origin. 70 samples were successfully analyzed with MLPA and we found one case with a microduplication in the 17p subtelomere for a frequency of 1,4%. Also,the karyotype was performed in 33cases, and we foundone case with a chromosome aberration that can be detect by microscope for a frequency of 3%. The subtelomeric chromosome aberration frequency was lower than expected as we compare our results with similar studies. Finally, with this work we conclude that the karyotype and the MLPA technique complement each other for approaching people with ID of unknown origin.


Subject(s)
Humans , Male , Female , Chromosome Aberrations , Intellectual Disability , Costa Rica
5.
Rev. chil. obstet. ginecol. (En línea) ; 87(2): 104-110, abr. 2022. ilus, tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1388716

ABSTRACT

INTRODUCCIÓN: La infertilidad es una enfermedad multicausal y el componente genético representa uno de sus principales eventos. Si bien la distribución de la infertilidad puede variar entre poblaciones, las parejas de los países con bajos y medianos ingresos pueden verse más afectadas por la infertilidad, con una proporción de alteraciones citogenéticas aún no esclarecidas. OBJETIVO: Evaluar la frecuencia de alteraciones citogenéticas y su correlación con el número de abortos en pacientes peruanas con diagnóstico de infertilidad. MÉTODO: Se realizó un estudio de corte transversal en 400 pacientes de 18 a 60 años, de ambos sexos, con diagnóstico de infertilidad. Se registraron las características clínicas disponibles durante el examen genético y el análisis citogenético convencional fue con bandeo GTG en muestras de sangre periférica. El análisis de correlación se realizó con la prueba de Spearman. RESULTADOS: Del total, 389 pacientes cumplieron los criterios de inclusión, y de estos, 169 (43,44%) tuvieron reportes de abortos (promedio: 2,25, rango: 1-7). Hallamos una correlación significativa ente el número de abortos y las alteraciones citogenéticas (p < 0,000). Reportamos 25/289 (6,43%) alteraciones cromosómicas, de las que 11/25 (44%) fueron heterocromatinas constitutivas y 6/25 (24%) fueron translocaciones reciprocas. Las alteraciones citogenéticas más frecuentes fueron 16qh+ y 9qh+ (ambas con un 16%), y afectaron a 17 (68%) varones. CONCLUSIONES: Existe una moderada frecuencia de alteraciones citogenéticas en pacientes peruanos con diagnóstico de infertilidad, y las alteraciones más frecuentes fueron heterocromatina constitutivas. Además, evidenciamos una correlación significativa ente el número de abortos y las alteraciones citogenéticas.


INTRODUCTION: Infertility is a multicausal disease and the genetic component represents one of its main events. Although the distribution of infertility may vary between populations, couples in low-and-middle-income countries may be more affected by infertility with a proportion of cytogenetic alterations still unclear. OBJECTIVE: To evaluate the frequency of cytogenetic alterations and their correlation with the number of abortions in Peruvian patients with a diagnosis of infertility. METHOD: A cross-sectional study was carried out in 400 patients between 18 and 60 years-old, of both genders with a diagnosis of infertility. The clinical characteristics available during the genetic examination were recorded and the conventional cytogenetic analysis was with GTG banding in peripheral blood samples. The correlation analysis was performed with the Spearman test. RESULTS: Of the total 389 patients who met the inclusion criteria, of these 169 (43.44%) patients had reports of abortions (mean: 2.25, range: 1-7). We found a significant correlation between the number of abortions and cytogenetic alterations (p < 0.000). We report 25/289 (6.43%) chromosomal alterations, where 11/25 (44%) were constitutive heterochromatin, and 6/25 (24%) were reciprocal translocations. The most frequent cytogenetic alterations were 16qh + and 9qh + (both 16%), and affected 17 (68%) men. CONCLUSIONS: There is a moderate frequency of cytogenetic alterations in Peruvian patients diagnosed with infertility, where the most frequent alterations were constitutive heterochromatin. Furthermore, we evidenced a significant correlation between the number of abortions and cytogenetic alterations.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Young Adult , Abortion, Spontaneous/epidemiology , Infertility/diagnosis , Infertility/genetics , Peru , Heterochromatin , Abortion, Spontaneous/genetics , Cross-Sectional Studies , Chromosome Aberrations , Cytogenetic Analysis , Abortion
6.
Rev. chil. obstet. ginecol. (En línea) ; 87(2): 97-103, abr. 2022. ilus, tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1388725

ABSTRACT

OBJETIVO: Analizar la implementación de la prueba rápida de reacción en cadena de la polimerasa cuantitativa y fluorescente (QF-PCR) para la detección de aneuploidías. MÉTODO: Se incluyeron todas las pacientes que se realizaron una QF-PCR entre septiembre de 2017 y mayo de 2021. En todos los casos se consignaron los datos clínicos, ecográficos y de laboratorio, y se efectuó un seguimiento de quienes se realizaron además cariograma y su resultado fue normal. RESULTADOS: Se realizaron 213 procedimientos invasivos genéticos prenatales, siendo 72 para detección rápida de aneuploidía mediante QF-PCR. El promedio de edad de las madres con QF-PCR fue de 37 años y 48 pacientes (67%) tenían menos de 15 semanas de gestación. La QF-PCR demostró aneuploidía de los cromosomas 18, 13 y de triploidía en 21 de 49 casos informados como anormales. De los 22 casos sin sugerencia de alteración, 17 accedieron a proseguir el estudio con cariotipo, que resultó anormal en 6 casos. Hubo 4 casos de discordancia entre la QF-PCR y el cariotipo, que pudo afectar el manejo clínico de la gestación. En 25/72 casos (34,7%) la aneuploidía era letal. CONCLUSIONES: Considerando la necesidad de tener un diagnóstico rápido, pero también completo y que permita un consejo genético apropiado, debería integrarse la QF-PCR a un protocolo de diagnóstico que considere variables clínicas y ecográficas.


OBJECTIVE: To analyze the performance of QF-PCR test for the detection of aneuploidies. METHOD: All patients who underwent QF-PCR from September 2017 to May 2021, were included. Clinical, ultrasound and laboratory data were recorded in all cases, as well as follow-up of the cases, including those performing karyotype and the result was normal. RESULTS: 213 prenatal genetic invasive procedures were performed in the study period, 72 for rapid detection of aneuploidy by QF-PCR. 48 patients (67%) were less than 15 weeks at the time of ultrasound diagnosis. The QF-PCR test demonstrated aneuploidy of chromosomes 18, 13, and triploidy in 21/49 cases reported as abnormal. Of the cases without suggestion of alteration (22), 17 agreed to continue the study with a karyotype, which was abnormal in 6 cases. There were 4 cases of discrepancy between QF-PCR and karyotype, which could affect the clinical management of pregnancy. 25/72 cases (34. 7%) corresponded to lethal aneuploidy. CONCLUSIONS: Our results justify the use of QF-PCR. Considering the need to have a rapid diagnosis, but also complete and that allows appropriate genetic counseling, it is that QF-PCR should be integrated into a protocol that considers clinical and ultrasound variables.


Subject(s)
Humans , Female , Pregnancy , Adult , Prenatal Diagnosis/methods , Polymerase Chain Reaction/methods , Aneuploidy , Chromosome Aberrations , Cytogenetic Analysis , Genetic Counseling
7.
Chinese Journal of Hematology ; (12): 336-341, 2022.
Article in Chinese | WPRIM | ID: wpr-935091

ABSTRACT

Objective: To retrospectively analyze the data of Chinese patients with newly diagnosed acute promyelocytic leukemia (APL) to preliminarily discuss the clinical and cytogenetic characteristics. Methods: From February 2004 to June 2020, patients with newly diagnosed APL aged ≥ 15 years who were admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College were chosen. Clinical and laboratory features were retrospectively analyzed. Results: A total of 790 cases were included, with a male to female ratio of 1.22. The median age of the patients was 41 (15-76) years. Patients aged between 20 and 59 predominated, with 632 patients (80%) of 790 patients classified as low and intermediate risk and 158 patients (20%) of 790 patients classified as high risk. The white blood cell, platelet, and hemoglobin levels at diagnosis were 2.3 (0.1-176.1) ×10(9)/L, 29.5 (2.0-1220.8) ×10(9)/L, and 89 (15-169) g/L, respectively, and 4.8% of patients were complicated with psoriasis. The long-form type of PML-RARα was most commonly seen in APL, accounting for 58%. Both APTT extension (10.3%) and creatinine>14 mg/L (1%) are rarely seen in patients at diagnosis. Cytogenetics was performed in 715 patients with newly diagnosed APL. t (15;17) with additional chromosomal abnormalities were found in 155 patients, accounting for 21.7%; among which, +8 was most frequently seen. A complex karyotype was found in 64 (9.0%) patients. Next-generation sequencing was performed in 178 patients, and 113 mutated genes were discovered; 75 genes had an incidence rate>1%. FLT3 was the most frequently seen, which accounted for 44.9%, and 20.8% of the 178 patients present with FLT3-ITD. Conclusions: Patients aged 20-59 years are the most common group with newly diagnosed APL. No obvious difference was found in the ratio of males to females. In terms of risk stratification, patients divided into low and intermediate risk predominate. t (15;17) with additional chromosomal abnormalities accounted for 21% of 715 patients, in which +8 was most commonly seen. The long-form subtype was most frequently seen in PML-RARα-positive patients, and FLT3 was most commonly seen in the mutation spectrum of APL.


Subject(s)
Adult , Aged , Chromosome Aberrations , Cytogenetics , Female , Humans , Leukemia, Promyelocytic, Acute/genetics , Male , Middle Aged , Mutation , Oncogene Proteins, Fusion/genetics , Retrospective Studies , Young Adult
8.
Chinese Journal of Hematology ; (12): 408-413, 2022.
Article in Chinese | WPRIM | ID: wpr-929628

ABSTRACT

Objective: To investigate the influence of the number of high-risk cytogenetic abnormalities (HRCA) on the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (MM) . Methods: A total of 360 patients with newly diagnosed MM admitted to Jiangsu Province Hospital between November 2013 and September 2020 were included in this study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was used to detect HRCA. Cytogenetic abnormalities were combined with clinical characteristics and outcomes for further analysis. Results: Among the 360 patients, 120 patients (33.3%) presented with no HRCAs, and 175 (48.6%) , 61 (16.9%) , and four (1.1%) patients had one, two, and three HRCA (s) , respectively. Patients were divided into three groups, including the no-HRCA group, one-HRCA group, and ≥two-HRCA group, according to the number of HRCAs. There were significant differences in the R-ISS stage, hemoglobin level, albumin level, and the proportion of bone marrow plasma cells among the three groups (P<0.05) . The COX proportional-hazards model identified extramedullary disease (P=0.018) , HRCA ≥ 2 (P=0.001) , and absence of autologous hematopoietic stem cell transplantation (P<0.001) as independent risk factors for progression free survival (PFS) and identified lactate dehydrogenase (LDH) level ≥ 220 U/L (P<0.001) , HRCA ≥2 (P=0.001) , and absence of autologous hematopoietic stem cell transplantation (P=0.005) as independent risk factors for overall survival (OS) . The median PFS was 28 months, 22 months, and 14 months (P=0.005) for the three cohorts, and their OS was not reached,60 months, and 30 months (P=0.001) , respectively. Conclusions: HRCA ≥ 2 is an independent risk factor for decreased survival in patients with newly diagnosed MM. More HRCAs result in heavier tumor burden, as well as a higher risk of disease progression and death.


Subject(s)
Chromosome Aberrations , Hematopoietic Stem Cell Transplantation , Humans , In Situ Hybridization, Fluorescence , Multiple Myeloma/genetics , Prognosis , Retrospective Studies , Transplantation, Autologous
9.
Article in Chinese | WPRIM | ID: wpr-928687

ABSTRACT

OBJECTIVE@#To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.@*METHODS@#Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).@*RESULTS@#Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.@*CONCLUSION@#There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.


Subject(s)
Chromosome Aberrations , Humans , In Situ Hybridization, Fluorescence , Multiple Myeloma/genetics , Mutation
10.
Article in Chinese | WPRIM | ID: wpr-928683

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics and prognosis of multiple myeloma patients with myelofibrosis.@*METHODS@#The clinical data of 263 patients with multiple myeloma (including 92 patients with myelofibrosis) treated in the department of hematology of our hospital from January 1, 2016 to June 31, 2020 were collected and retrospectively analyzed, the patients were divided into combined group and uncombined group. The MM stage, MM type, genetic characteristics and therapeutic effect of the patients in combined group and uncombined group were observed, and the relationship between the curative effect and the degree of myelofibrosis change of the patients in combined group was analyzed.@*RESULTS@#There was no statistically difference in the MM staging and classification between multiple myeloma patients with or without myelofibrosis (P>0.05). The positive rate of FISH results of the patients in combined group was significantly higher than those in uncombined group, and was significantly correlated to 1q21 amplification, D13S319 deletion, and IgH breakage (P<0.05). After treatment, the effective rate of the patients in uncombined group was significantly higher than those in combined group, and the degree of fibrosis in the effective patients in combined group was significantly reduced.@*CONCLUSION@#The survival rate of the patients with multiple myeloma complicated with myelofibrosis is shorter than that of the patients without myelofibrosis, and the overall prognosis is poor.


Subject(s)
Chromosome Aberrations , Humans , Multiple Myeloma/complications , Primary Myelofibrosis/complications , Prognosis , Retrospective Studies
11.
Asian Journal of Andrology ; (6): 248-254, 2022.
Article in English | WPRIM | ID: wpr-928551

ABSTRACT

Apparently balanced chromosomal structural rearrangements are known to cause male infertility and account for approximately 1% of azoospermia or severe oligospermia. However, the underlying mechanisms of pathogenesis and etiologies are still largely unknown. Herein, we investigated apparently balanced interchromosomal structural rearrangements in six cases with azoospermia/severe oligospermia to comprehensively identify and delineate cryptic structural rearrangements and the related copy number variants. In addition, high read-depth genome sequencing (GS) (30-fold) was performed to investigate point mutations causative of male infertility. Mate-pair GS (4-fold) revealed additional structural rearrangements and/or copy number changes in 5 of 6 cases and detected a total of 48 rearrangements. Overall, the breakpoints caused truncations of 30 RefSeq genes, five of which were associated with spermatogenesis. Furthermore, the breakpoints disrupted 43 topological-associated domains. Direct disruptions or potential dysregulations of genes, which play potential roles in male germ cell development, apoptosis, and spermatogenesis, were found in all cases (n = 6). In addition, high read-depth GS detected dual molecular findings in case MI6, involving a complex rearrangement and two point mutations in the gene DNAH1. Overall, our study provided the molecular characteristics of apparently balanced interchromosomal structural rearrangements in patients with male infertility. We demonstrated the complexity of chromosomal structural rearrangements, potential gene disruptions/dysregulation and single-gene mutations could be the contributing mechanisms underlie male infertility.


Subject(s)
Azoospermia/genetics , Chromosome Aberrations , Humans , Infertility, Male/genetics , Male , Oligospermia/genetics , Translocation, Genetic
12.
Article in Chinese | WPRIM | ID: wpr-928455

ABSTRACT

OBJECTIVE@#To investigate the parental-origin verification of fetal CNVs in the setting of prenatal diagnosis.@*METHODS@#182 families were recruited in this study. All the pregnant women underwent transabdominal amniocentesis or cordocentesis, and the amniotic fluid or cord blood samples were then subjected to karyotyping and chromosomal microarray analysis (CMA) respectively. The peripheral blood specimens of fetal parents were also tested by CMA for determining the parental-origin of fetal CNVs. Then we followed up the clinical outcomes of the fetuses.@*RESULTS@#Of the 182 fetuses, 163 (89.6%) had parental-origin CNVs, and 19 (10.4%) had de novo CNVs. 149 (91.4%) of the parental-origin CNVs were classified into the variant of uncertain significance (VUS) before parental-origin tests. After parental source verification, 137 (91.9%) of these VUS cases were changed into likely benign cases. Among the 163 cases of parental-origin CNVs, 122 (74.8%) fetuses were born healthy. Among the 19 de novo cases, 9 of these families chose to terminate the pregnancy.@*CONCLUSION@#The majority of inherited CNVs detected by CMA had a tendency to be benign, and the parental source verification could assist the elucidation of clinical significance of CNVs in prenatal diagnosis.


Subject(s)
Chromosome Aberrations , DNA Copy Number Variations , Female , Humans , Karyotyping , Microarray Analysis , Parents , Pregnancy , Prenatal Diagnosis
13.
Article in Chinese | WPRIM | ID: wpr-928439

ABSTRACT

OBJECTIVE@#To analyze the genomic variation characteristics of fetal with abnormal serological screening, and to further explore the value of copy number variation (CNV) detection technology in prenatal diagnosis of fetal with abnormal serological screening.@*METHODS@#7617 singleton pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal Down's serological screening were selected. According to the results of serological screening, the patients were divided into high risk group, borderline risk group and single abnormal multiple of median (MOM) group. CMA and CNV-Seq were used to detect the copy number variation of amniotic fluid cell genomic DNA and combined with amniotic fluid cell karyotype analysis for prenatal diagnosis. Outpatient revisit combined with telephone inquiry was used for postnatal follow-up.@*RESULTS@#Among 7617 amniotic fluid samples, aneuploidy was detected in 138cases (1.81%) by CMA and CNV-Seq, 9 cases of aneuploid chimerism were detected by amniotic fluid cell karyotype analysis, and 203 cases of fetus carrying pathogenic and likely pathogenic CNV (P/LP CNV) were detected, the variant of uncertain significance (VUS) was detected in 437 cases (5.7%), the overall abnormal detection rate was 10.33%. The detection rate of aneuploidy by CMA and CNV-Seq in three group were 123 cases (2.9%), 13 cases (1.3%) and 2 cases (0.4%), respectively,and showing no significant difference (χ 2=7.469, P=0.024). The detection rate of pathogenic and likely pathogenic CNV in three group were 163cases (2.6%); 24 cases (2.6%) and 16 cases (3.3%), respectively, and showing no significant difference (χ 2=0.764, P=0.682). The CMA reported 2.9% (108/3729)P/LP CNV, and CNV-seq reported 2.4% (95/3888)P/LP CNV, both tests showed similar detective capabilities (χ 2=1.504, P=0.22).The most popular P/LP CNV in this cohort were Xp22.31 microdeletion, 16p13.11 microduplication /microdeletion, 22q11.21 microduplication /microdeletion. In fetuses with P/LP CNV CNV, 59 fetuses were terminated pregnancy, and 32 of 112 fetuses born had abnormal clinical manifestations. Non-medically necessary termination of pregnancy occurred in 11 fetuses carrying VUS CNV, 322 fetuses carrying VUS CNV were born, 4 of them presented abnormal clinical manifestations.@*CONCLUSION@#Compared with the traditional chromosome karyotype, CMA and CNV-Seq can improve the detection rate of pathogenic and likely pathogenic CNV. CMA and CNV-seq can be used for first tier diagnosis of pregnant women in the general population with abnormal Down's serological screening.


Subject(s)
Amniotic Fluid , Aneuploidy , Chromosome Aberrations , DNA Copy Number Variations , Female , Genomics , Humans , Pregnancy , Pregnancy Trimester, Second , Pregnant Women , Prenatal Diagnosis/methods , Technology
14.
Article in Chinese | WPRIM | ID: wpr-928420

ABSTRACT

OBJECTIVE@#To assess the value of copy number variation sequencing (CNV-seq) and karyotyping in the prenatal diagnosis for carriers of balanced translocations.@*METHODS@#Clinical records of 135 amniocentesis samples of balanced translocation carriers undergoing simultaneous CNV-seq and karyotyping were analyzed. Chromosomal aberrations were defined as those can definitely lead to birth defects definitely, which included chromosomal numerical abnormality, large deletion/duplication and pathogenic copy number variations (pCNVs).@*RESULTS@#The detection rates for karyotyping and CNV-seq were 4.44% (6/135) and 5.93% (8/135) respectively, and the latter had a detection rate of 1.48(2/135) higher than the former. A total of 68 fetal chromosomal translocations were detected by karyotying analysis.@*CONCLUSION@#For couples carrying a balanced translocation, simultaneous CNV-seq and karyotyping is conducive to the detection of fetal chromosomal abnormalities and genetic counseling.


Subject(s)
Chromosome Aberrations , Chromosome Disorders/genetics , DNA Copy Number Variations , Female , Humans , Karyotyping , Pregnancy , Prenatal Diagnosis , Translocation, Genetic
15.
Article in Chinese | WPRIM | ID: wpr-928770

ABSTRACT

Multiple myeloma (MM) is a kind of hematologic malignancy occurring in plasma cells. Cytogenetic technique plays an important role in risk stratification of MM. 1q21 amplification is one of the common chromosomal abnormalities in MM. Studies have shown that 1q21 amplification is associated with poor prognosis in MM patients. At present, with the development of new drugs, cellular immunotherapy, and improvement of hematopoietic stem cell transplantation technology, the remission depth and survival time of MM significantly increased. Rapid and accurate identification of high-risk patients and individualized treatment according to the patient's condition is the key to improve the therapeutic effect of MM. This article reviews the mechanism of 1q21 amplification in MM and the efficacy of new drugs in the treatment of MM with 1q21 chromosome amplification.


Subject(s)
Chromosome Aberrations , Chromosomes , Chromosomes, Human, Pair 1/genetics , Hematopoietic Stem Cell Transplantation , Humans , Multiple Myeloma/drug therapy , Prognosis
16.
Rev. chil. obstet. ginecol. (En línea) ; 86(4): 390-396, ago. 2021. ilus, tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1388675

ABSTRACT

INTRODUCCIÓN: Las anomalías congénitas de los riñones y las vías urinarias (CAKUT, Congenital Anomalies of the Kidney and Urinary Tract) representan un 20-30% de las anomalías detectadas en el periodo prenatal. Si bien la mayoría son de buen pronóstico, un 25% se asocian a enfermedad renal crónica en la infancia y en los casos graves a mortalidad perinatal. OBJETIVO: Describir los casos ingresados al Centro de Referencia Perinatal Oriente (CERPO) y determinar los resultados perinatales y la sobrevida al año. MÉTODO: Estudio descriptivo y retrospectivo. Se incluyeron pacientes ingresadas en la base de datos CERPO, entre los años 2003 y 2019, con diagnóstico de anomalía nefrourológica. Se incluyeron antecedentes prenatales, perinatales y de seguimiento posnatal al año. RESULTADOS: Se evaluaron 273 pacientes. La edad gestacional promedio de derivación fue de 29 semanas + 2 días. El diagnóstico más frecuente fueron las anomalías del tracto de salida (69%). Un 40% de los casos se asociaron a otras anomalías congénitas, siendo las cardiopatías las más frecuentes (19%). Aceptaron la realización de estudio genético invasivo 38 pacientes, de las cuales un 34% presentaron aneuploidías, siendo las trisomías 18 y 13 las más frecuentes (17% y 6%, respectivamente). Se instalaron cinco shunts derivativos vesicoamnióticos en fetos diagnosticados con megavejiga. La sobrevida global para la patología nefrourológica fue del 63% al año, y la mortalidad fetal y neonatal fue del 7% y el 16%, respectivamente. La sobrevida al año según el grupo de clasificación CAKUT fue del 22% para las anomalías de número de riñones, del 46% para las anomalías de tamaño y de morfología renal, del 60% para las anomalías de la posición renal y del 72% para las anomalías del tracto de salida. En este último grupo, la sobrevida alcanza el 81% al excluir los pacientes con diagnóstico prenatal de megavejiga, que presentaron una sobrevida al año del 28%. Los casos de patología nefrourológica asociada a oligohidramnios (índice de líquido amniótico < 5 cm) sin evidencias de uropatía obstructiva asociada presentaron una sobrevida al año del 3%. CONCLUSIONES: Las anomalías del sistema nefrourológico son un diagnóstico prenatal frecuente. La sobrevida al año fue del 63%, pero es necesario prolongar el seguimiento a largo plazo para determinar la evolución de la función renal en cada diagnóstico. La asociación de patología nefrourológica y oligohidramnios conlleva una sobrevida menor.


INTRODUCTION: Congenital anomalies of the kidneys and urinary tract (CAKUT) represent 20 to 30% of the anomalies detected prenatally. Although most are of good prognosis, 25% are associated with chronic kidney disease in childhood and severe cases with perinatal mortality. OBJECTIVE: To describe the cases studied in the Eastern Perinatal Referral Center (CERPO) and to determine the perinatal outcome and survival at one year. METHOD: Descriptive and retrospective study. Patients registered on the CERPO database, between 2003 to 2019, with diagnosis of nephrourological anomaly were included. Antenatal, perinatal and postnatal follow-up information was collected. RESULTS: 273 patients were evaluated. The average gestational age at referral was 29 + 2 weeks. The main diagnosis was urinary tract outlet disorders (69%). Thirty nine percent of the cases were associated with other congenital anomalies, with heart disease being the most frequent (19%). Thirty-eight patients accepted an invasive procedure for genetic study, 34% presented aneuploidy, trisomy 18 and 13 were the most frequent (17% and 6% respectively). Five vesico-amniotic derivative shunts were installed in fetuses diagnosed with megabladder. Overall survival at one year was 63% and fetal and neonatal mortality were 7% and 16% respectively. One-year survival per group according to CAKUT classification was 22% in kidney number abnormalities, 46% in kidney size and morphology abnormalities, 60% in renal position abnormalities and 72% in outflow tract abnormalities. In the latter, survival reaches 81% excluding the patients with prenatal diagnosis of megabladder who had a one-year survival of 28%. The cases of nephrourological pathology associated with oligohydramnios (amniotic fluid index < 5 cm) without evidence of associated obstructive uropathy presented a survival of 3% at one year. CONCLUSIONS: The anomalies of the nephrourological system correspond to a frequent prenatal diagnosis. Overall, the one-year survival was 63%; however, follow-up must continue to determine the evolution of renal function in relation to each diagnosis.


Subject(s)
Humans , Female , Pregnancy , Prenatal Diagnosis , Urogenital Abnormalities/diagnosis , Kidney/abnormalities , Prognosis , Urogenital Abnormalities/classification , Urologic Diseases/diagnosis , Chile , Retrospective Studies , Chromosome Aberrations , Kidney Diseases/diagnosis
17.
J. pediatr. (Rio J.) ; 97(3): 321-328, May-June 2021. tab
Article in English | LILACS | ID: biblio-1279326

ABSTRACT

Abstract Objective This article presents a clinical and cytogenomic approach that focuses on the diagnosis of syndromic oral clefts (OCs). Methods The inclusion criteria were individuals with OC presenting four or more minor signs and no major defects (non-syndromic oral clefts [NSOCs]) as well as individuals with OC presenting at least another major defect, regardless of the number of minor signs (syndromic oral clefts [SOCs]). The exclusion criteria included NSOC with less than four minor signs, SOC with known etiology, as well as atypical oral clefts. Results Of 1647 individuals with OC recorded in the Brazilian Database of Craniofacial Anomalies, 100 individuals were selected for chromosome microarray analysis (CMA). Among these, 44 individuals were clinically classified as NSOC and 56 as SOC. CMA was performed for both groups, and abnormal CMA was identified in 9%, all previously classified as SCO. The clinical and CMA data analyses showed a significant predominance of abnormal CMA in individuals classified as SOC (p = 0.0044); prematurity, weight, length, and head circumference at birth were significantly lower in the group with abnormal CMA. Besides, minor signs were significantly higher in this group (p = 0.0090). Conclusion The rigorous selection of cases indicates that the significant variables could help in early recognition of SOC. This study reinforces the importance of applying the CMA technique to establish the diagnosis of SOC. This is an important and universal issue in clinical practice for intervention, care, and genetic counseling.


Subject(s)
Humans , Cleft Lip/genetics , Cleft Palate/genetics , Brazil , Chromosome Aberrations , Genomics
18.
Rev. bras. ginecol. obstet ; 43(6): 452-456, June 2021. tab, graf
Article in English | LILACS | ID: biblio-1341140

ABSTRACT

Abstract Objective The objective of the present study was to determine the frequency of malformations and chromosomal abnormalities in a population of fetuses with an aberrant right subclavian artery (ARSA). Methods This is a 6-year retrospective study of fetuses with a prenatal diagnosis of ARSA conducted during the period between September 2013 and June 2019 at a fetal medicine unit. Data were collected from ultrasound, fetal echocardiograms, genetic studies, and neonatal records. Results An ARSA was diagnosed in 22 fetuses. An ARSA was an isolated finding in 18 out of 22 cases (82%). Associated abnormal sonographic findings were found in 4 cases. All cases underwent invasive testing. In 1 of the cases, a chromosomal abnormality was detected (mos 45,X [13]/46,X,e(X) (p22.1q22.1)). No cases of congenital heart disease were found in any of these fetuses. There were two cases in which the postnatal evaluation revealed amalformation: one case of hypospadias and 1 case of cleft palate. Conclusion The presence of an isolated ARSA is benign and is not associated with chromosomal abnormalities. The finding of ARSA, however, warrants a detailed fetal ultrasound in order to exclude major fetal abnormalities and other soft markers.


Resumo Objetivo O objetivo do presente estudo foi determinar a frequência demalformaçães e anomalias cromossômicas em uma população de fetos com artéria subclávia direita aberrante (ARSA). Métodos Este é um estudo retrospectivo de 6 anos de fetos com diagnóstico prénatal de ARSA realizado durante o período de setembro de 2013 a junho de 2019 em uma unidade de medicina fetal. Os dados foram coletados de ultrassom, ecocardiograma fetal, estudos genéticos e registros neonatais. Resultados Um ARSA foi diagnosticado em 22 fetos. Um ARSA foi um achado isolado em 18 dos 22 casos (82%). Achados ultrassonográficos anormais associados foram encontrados em 4 casos. Todos os casos foram submetidos a testes invasivos. Em um dos casos, foi detectada uma anormalidade cromossômica (mos 45, X [13] / 46, X, e (X) (p22.1q22.1)). Nenhum caso de doença cardíaca congênita foi encontrado em qualquer um desses fetos. Houve dois casos em que a avaliação pós-natal revelou a malformação: um caso de hipospádia e 1 caso de fenda palatina. Conclusão A presença de ARSA isolado é benigna e não está associada a anormalidades cromossômicas. O achado de ARSA, no entanto, justifica uma ultrassonografia fetal detalhada para excluir anormalidades fetais importantes e outros marcadores leves.


Subject(s)
Humans , Male , Female , Pregnancy , Adolescent , Adult , Young Adult , Subclavian Artery/abnormalities , Congenital Abnormalities/diagnosis , Ultrasonography, Prenatal , Chromosome Aberrations , Cardiovascular Abnormalities/genetics , Cardiovascular Abnormalities/diagnostic imaging , Subclavian Artery/diagnostic imaging , Echocardiography , Genetic Testing , Retrospective Studies
19.
Biomédica (Bogotá) ; 41(2): 302-313, abr.-jun. 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1339269

ABSTRACT

Resumen | Introducción. La leucemia mieloide aguda es una neoplasia heterogénea caracterizada por la proliferación de células mieloides inmaduras. El análisis citogenético ha revelado la presencia de aberraciones cromosómicas de importancia en el pronóstico del paciente. Objetivo. Determinar los grupos de riesgo citogenético de pacientes pediátricos con leucemia mieloide aguda a partir de la supervivencia global. Materiales y métodos. Se hizo un estudio observacional de corte transversal. Se incluyeron los registros clínicos de los pacientes pediátricos con diagnóstico de leucemia mieloide aguda de novo admitidos en el Instituto Nacional de Enfermedades Neoplásicas entre el 2001 y el 2011 y sometidos a análisis citogenético de médula ósea. Los grupos de riesgo citogenético se establecieron según los criterios del Medical Research Council. Las curvas de supervivencia global se elaboraron con el método de Kaplan-Meier y se compararon mediante la prueba de Mantel-Cox y una regresión de Cox, utilizando el programa R, versión 3.3.2. Resultados. Se incluyeron 130 pacientes, 68 varones (52,3%) y 62 mujeres (47,7%), mayoritariamente del subtipo M2 (33%). La edad promedio fue de 7,7 (rango de 0 a 15 años). Se observaron aberraciones cromosómicas en el 60,8% y la más frecuente fue la traslocación t(8;21). Según el análisis de supervivencia global, se observaron dos grupos de riesgo citogenético: favorable y desfavorable. Conclusión. Se determinaron dos grupos de riesgo citogenético: alto (o desfavorable) y estándar (o favorable).


Abstract | Introduction: Acute myeloid leukemia is a heterogeneous disorder characterized by immature myeloid cell proliferation. Cytogenetic analysis has revealed the presence of chromosomal aberrations important to patient prognosis. Objective: To determine cytogenetic risk groups of pediatric patients with acute myeloid leukemia according to overall survival. Materials and methods: In this cross-sectional observational study, the clinical records of pediatric patients diagnosed with de novo acute myeloid leukemia admitted to the Instituto Nacional de Enfermedades Neoplásicas between 2001 and 2011 with cytogenetic analysis of bone marrow were included. Cytogenetic risk groups were established according to the criteria of the Medical Research Council. Overall survival curves were generated with the Kaplan-Meier method and compared using the Mantel-Cox test and Cox regression with the software R, version 3.3.2. Results: A total of 130 patients were included, 68 males (52.3%) and 62 females (47.7%), most of them with subtype M2 (33%). The average age was 7.7 years (range: 0-15 years). Chromosomal aberrations were observed in 60.8% of the patients, the most frequent of which was the translocation t(8;21). According to the overall survival analysis, two cytogenetic risk groups were established: favorable and unfavorable. Conclusion: Two groups of cytogenetic risk were determined: high (or unfavorable) and standard (favorable).


Subject(s)
Pediatrics , Leukemia, Myeloid, Acute , Survival , Chromosome Aberrations , Cytogenetic Analysis , Karyotype
20.
Rev. argent. salud publica ; 13: 1-8, 5/02/2021.
Article in Spanish | LILACS, BINACIS, ARGMSAL | ID: biblio-1147271

ABSTRACT

INTRODUCCIÓN: Las cardiopatías congénitas (CC) son causadas por el desarrollo anómalo del corazón durante el período embriofetal. Abarcan un amplio espectro de anomalías estructurales de las cavidades cardíacas o de los grandes vasos, con una prevalencia mundial de 6 a 9 por 1000 nacimientos. En Argentina constituyen un tercio de las anomalías congénitas (AC) al nacimiento. Si bien su etiología es heterogénea, se ha observado recurrencia familiar acorde con la influencia de factores genéticos. El objetivo del estudio fue evaluar la presencia de anomalías cromosómicas, desbalances genómicos o variantes de secuencias en una muestra de niños afectados con CC en Argentina. MÉTODOS: Se incluyó a 289 pacientes con CC de hasta 16 años. Se realizó un cariotipo para pacientes con otras AC y análisis por amplificación múltiple de sondas dependiente de ligación (MLPA) de regiones genómicas asociadas a CC para aquellos con CC conotroncales. En muestras seleccionadas, se analizaron desbalances genómicos por microarreglos de ADN (array-CGH) o variantes de secuencia en el gen NKX2-5. RESULTADOS: Hubo 9 pacientes que presentaron anomalías cromosómicas, 21 desbalances por MLPA y 8 por array-CGH. No se hallaron variantes patogénicas en NKX2-5 en los casos estudiados. DISCUSIÓN: Se halló la causa de la afección en el 13% de los casos analizados. El estudio de pacientes con CC aisladas o asociadas a otras AC no había sido abordado previamente en Argentina mediante este algoritmo


Subject(s)
Chromosome Aberrations , Genetics, Medical , Heart Diseases
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