Hallazgos citogenéticos y edad materna en pacientes con síndrome down en un hospital de referencia pediátrico en el Perú

Introducción: El síndrome Down es un trastorno congénito originado por una trisomía total o parcial del cromosoma 21 y es considerada la causa genética más común de malformaciones congénitas y discapacidad intelectual. El objetivo de este estudio fue describir las alteraciones citogenéticas de pacientes con Síndrome Down y su relación con la edad materna. Métodos: Estudio transversal, descriptivo-analítico. Se incluyó 436 pacientes con Síndrome Down admitidos en el Instituto Nacional de Salud del Niño durante el período 2017-2019. Se analizaron las variables: alteración citogenética y edad materna. Resultados: Se encontró que el 99,3% (n=433) de pacientes presentaron algún tipo de alteración citogenética y tres pacientes presentaron cariotipo normal. La edad de los pacientes al momento de la toma de muestra estuvo comprendida entre los 0,03 y 17 años, la relación masculino/femenino fue de 1.2:1. La alteración citogenética más frecuente fue la trisomía 21 libre (94,7%), seguida por la translocación Robertsoniana (n=16) y el mosaicismo (n=6). En el caso de la edad materna se encontró una mediana de 37 años (rango: 13-47). Conclusiones: La trisomía 21 libre es la alteración citogenética más común en Síndrome Down; sin embargo, la translocación Robertsoniana y los mosaicismos fueron más frecuentes en edad materna menor de 35 años, sugiriendo que existe otros factores de riesgo diferentes a la edad materna avanzada en este grupo etario.

Introduction: Down syndrome is a congenital disorder caused by a total or partial trisomy of chromosome 21 and is considered the most common genetic cause of congenital malformations and intellectual disability. The objective of this study was to describe the cytogenetic alterations of patients with Down syndrome and their relationship with maternal age. Methods: Cross-sectional, descriptive-analytical study. 436 patients with Down syndrome admitted to the Instituto Nacional de Salud del Niño during the 2017-2019 period were included. The variables analyzed were: cytogenetic diagnosis and maternal age. Results: It was found that 99,3% (n=433) of patients presented some type of cytogenetic alteration and three patients presented a normal karyotype. The age of the patients at the time of sampling was between 0,03 and 17 years, the male/female ratio was 1.2:1. The most frequent cytogenetic alteration was free trisomy 21 (94,7%), followed by Robertsonian translocation (n=16) and mosaicism (n=6). In the case of maternal age, a median of 37 years was found (range: 13-47). Conclusions: Free trisomy 21 is the most common cytogenetic condition in Down syndrome; however, the Robertsonian translocation and mosaicisms were more frequent in patients whose mothers were les than 35 years old, suggesting that there are other risk factors than advanced maternal age in this group.

Analysis of cytogenetic characteristics of primary childhood B-cell acute lymphoblastic leukemia and risk factors for first treatment response / 白血病·淋巴瘤

Objective:To investigate the cytogenetic characteristics and influencing factors associated with first treatment response in primary childhood B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 49 children with primary B-ALL who were admitted to the First Hospital of Xiamen University from April 2019 to September 2021 were retrospectively collected, and the clinical characteristics, cytogenetic and molecular biology findings and other clinical indicators before and after treatment were obtained. Genotyping, clinical risk stratification after the first induction chemotherapy and chemotherapy regimen development were performed according to the pediatric ALL treatment specification (2018 version). The relationship between different genotypes and clinical indicators in children with B-ALL was analyzed, and the correlation between clinical risk stratification and each indicator was analyzed by Spearman rank correlation analysis.Results:The median age of 49 children was 3.0 years old (interquartile range: 3.2 years old), 32 cases (65.3%) were male and 17 cases (34.7%) were female, with a male-to-female ratio of 1.88∶1. Thirty-five cases (71.4%) had gene mutations before treatment and 14 cases (28.6%) had no mutations. Among the 35 cases with mutations, E2A-PBX1 was found in 5 cases (10.2%), including 1 case with Philadelphia chromosome (Ph)-like; IKZF1 deletion was found in 8 cases (16.3%), including 4 cases with Ph-like, 1 case with Ph-positive, and 1 case with MLL rearrangement; MLL rearrangement was found in 3 cases (6.1%); Ph-like alone was found in 12 cases (24.5%); TEL-AML1 was found in 6 cases (12.2%), including 2 cases with Ph-like; 1 case (2.0%) with Ph-positive alone. The clinical risk stratification showed that 7 cases (14.3%) had high risk, 28 cases (57.1%) had intermediate risk, and 14 cases (28.6%) had low risk. The proportions of patients with high and intermediate clinical risk before induction chemotherapy [20.0% (7/35) vs. 0.0% (0/14), 62.9% (22/35) vs. 42.9% (6/14)] and the proportion of patients with altered mutation status on day 33 of induction chemotherapy [42.9% (15/35) vs. 0.0% (0/14)] were higher in patients with mutations before induction chemotherapy than those in patients without gene mutations before treatment (all P < 0.01). The gene mutation or not before treatment was not correlated with gender, white blood cell count at first diagnosis, hormone sensitivity, minimal residual disease (MRD) from the 15th to the 19th day of induction chemotherapy, and MRD on the 33rd day of induction chemotherapy (all P > 0.05). Clinical risk stratification of children was associated with white blood cell count at first diagnosis ( r = 0.392, P = 0.005), neutrophil count ( r = 0.453, P = 0.001), lymphocyte count ( r = 0.418, P = 0.001), monocyte count ( r = 0.359, P = 0.017), blood uric acid level ( r = 0.378, P = 0.007), and proportion of bone marrow naive lymphocyte count before treatment ( r = 0.316, P = 0.027) and from 15th to the 19th day of induction chemotherapy ( r = 0.399, P = 0.005) and the 33rd day of induction chemotherapy ( r = 0.408, P = 0.028), proportion of children with bone marrow MRD ≥ 0.000 1 on the 33rd day of induction chemotherapy ( χ2 = 15.42, P < 0.001), and proportion of children with gene mutations before treatment ( χ2 = 9.10, P = 0.005). Conclusions:High levels of leukocytes, neutrophils, lymphocytes, monocytes, naive lymphocytes, blood uric acid, and naive lymphocytes from the 15th to the 19th day and the 33rd day of chemotherapy, MRD on the 33rd day of chemotherapy and genotype in children with B-ALL may be associated with poor response to treatment. Clinical risk stratification is associated with gene mutation status, and gene mutation may be an important indicator of treatment response in children with B-ALL.

Application of targeted capture high depth sequencing and transcriptome sequencing in childhood B-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To investigate the differences among targeted capture high depth sequencing (Panel-seq), transcriptome sequencing (RNA-seq) and traditional detection methods in cytogenetic and molecular genetic typing of childhood B-cell acute lymphoblastic leukemia (B-ALL) and their significances.Methods:The clinical data of 152 newly diagnosed childhood B-ALL cases in Guangzhou Women and Children's Medical Center from September 2020 to December 2021 were retrospectively analyzed. Along with traditional cytogenetic and molecular detection methods including karyotyping, fluorescence in situ hybridization (FISH) and 43 kinds of fusion gene quantitative screening for traditional cells and molecular genetic detection, both Panel-seq and RNA-seq were also performed. Panel-seq covered more than 600 genes with common mutations in hematological tumors, from which fusion genes and gene mutations were both analyzed. RNA-seq was used to analyze fusion genes, gene mutations, gene expression, and copy number variation at the chromosome level. High hyperdiploid karyotype was estimated by using gene expression profile clustering and copy number variations. The cytogenetic typing results of all detection methods were also analyzed.Results:Among 152 patients, 93 cases were males and 59 cases were females, with the median age of 4.0 years (0.8-13.0 years). The median blast cell ratio was 0.855 (0.215-0.965). The traditional detection methods could identify 4 cases (2.6%) with BCR-ABL1, 2 cases (1.3%) with CRLF2 gene-related fusion, 27 cases (17.8%) with ETV6-RUNX1, 1 case (0.7%) with iAMP21, 5 cases (3.3%) with MLL rearrangement, 8 cases (5.3%) with TCF3-PBX1 and 22 cases (14.5%) with high hyperdiploid karyotype. Panel-seq could identify 4 cases (2.6%) with BCR-ABL1, 2 cases (1.3%) with CRLF2 gene-related fusions, 27 cases (17.8%) with ETV6-RUNX1, 3 cases (2.0%) with MEF2D gene-related fusions, 1 case (0.7%) with MEIS1-FOXO1, 5 cases (3.3%) with MLL rearrangement, 5 cases (3.3%) with PAX5 gene-related fusions, 8 cases (5.3%) with TCF3-PBX1 fusions, 4 cases (2.6%) with ZNF384 gene-related fusions, and 2 cases (1.3%) with IKZF1 N159Y mutations. Among 152 patients, 1 case with MLL rearrangement didn't receive RNA-seq detection because of sample quality; in other 151 B-ALL cases, 1 case (0.7%) with ACIN1-NUTM1, 4 cases (2.6%) with BCR-ABL1, 3 cases (2.0%) with CRLF2 gene-related fusions, 8 cases (5.3%) with DUX4 gene-related fusions, 27 cases (17.9%) with ETV6-RUNX1, 3 cases (2.0%) with MEF2D gene-related fusions, 1 case (0.7%) with MEIS1-FOXO1, 4 cases (2.6%) with MLL rearrangement, 5 cases (3.3%) with PAX5 gene-related fusions, 1 case (0.7%) with ZMIZ1-ABL1, 8 cases (5.3%) with TCF3-PBX1,4 cases (2.6%) with ZNF384 gene-related fusions, 61 cases (40.4%) with hyperdiploid karyotypes, and 2 cases (1.3%) with IKZF1 N159Y mutations were detected; RNA-seq had obvious advantage in detecting fusion gene and hyperdiploid karyotype. The cytogenetic and molecular genetic typing rates of traditional method, Panel-seq and RNA-seq were 45.4% (69/152), 40.1% (61/152) and 87.4% (132/151), respectively. The combination of the three could identify 89.5% (136/152) of childhood B-ALL patients.Conclusions:The combination of Panel-seq and RNA-seq can increase the detection rate of genetic abnormality in childhood B-ALL, which provides a more accurate molecular genetic classification for B-ALL and the basis for treatment guideline and prognosis judgement.

Molecular profile of patients with myelofibrosis: a 10-year experience

ABSTRACT Objective To analyze the karyotype test and myeloid panel with next-generation sequencing findings in patients with myelofibrosis, and to compare transplant characteristics in patients referred for bone marrow transplantation. Methods Retrospective, single-center study with patients diagnosed with myelofibrosis treated at Hospital Israelita Albert Einstein between 2010 and 2020. Results A total of 104 patients with myelofibrosis were examined. Patients who had not been submitted to tests in our service were excluded. The final sample comprised 69 patients. Of these 69, 56 were submitted to karyotyping and 22 to myeloid panel with next-generation sequencing. Karyotype was normal in 60% of the patients and altered in 40%. The prevalence of high-risk molecular mutations was higher in patients referred for bone marrow transplantation (100% versus 50%). The median follow-up of transplant patients was 2.4 years and the overall survival at 2 years was 80% (95%CI: 62-100%). Conclusion The molecular analysis enables estimating the patient's risk and thus instituting more aggressive treatment such as bone marrow transplant for patients at higher risk, being a relevant tool to guide therapy. Given the significance of molecular analysis for therapeutic decision-making in myelofibrosis, collection and disclosure of data on the prevalence of cytogenetic changes and findings of next-generation sequencing in affected patients is important.

Indications for prenatal diagnosis and pregnancy outcomes of Turner syndrome with different karyotypes in 205 cases / 中华围产医学杂志

Objective:To investigate the indications for prenatal diagnosis and pregnancy outcomes of fetal Turner syndrome (TS) with different karyotypes.Methods:Clinical data of TS cases diagnosed by fetal karyotyping in the Prenatal Diagnostic Center of Guangzhou Women and Children′s Medical Center from January 1, 2010, to June 30, 2021, were analyzed retrospectively. According to the karyotyping results, these cases were divided into two groups: monosomy X (45,X) and non-monosomy X groups (including karyotypes of mosaic monosomy X, isochromosome X, X deletion, X rearrangement, pseudodicentric X, and mosaicism with Y or Y deletion). Chi-square test was used to compare the detection rate, indications for prenatal diagnosis, and pregnancy outcomes of the two groups, and the Bonferroni test was conducted for further pairwise comparisons between the subgroups. The Chi-square test (or Fisher's exact test) was used to compare the abnormal ultrasound signs. Mann-Whitney U test was used to compare the nuchal translucency (NT) thickness of the two groups. Results:(1) Invasive prenatal diagnosis was performed on 27 981 pregnancies, and 205 (0.73%) of them were diagnosed with TS, including 135 cases of monosomy X and 70 cases of non-monosomy X (44 with numerical sex chromosome abnormalities, and 26 with structural sex chromosome abnormalities). (2) Out of the 205 pregnancies, 164 (80.0%) had one indication for prenatal diagnosis, and 41 (20.0%) had multiple indications. The detection rate of fetal ultrasonographic abnormalities [85.2% (115/135)] in monosomy X cases was significantly higher than that of three other indications [positive serological screening for Down's syndrome: 67.3% (35/52); positive non-invasive prenatal testing (NIPT) for sex chromosome abnormality: 60.0% (15/25); and other indications (advanced maternal age, adverse pregnancy history and thalassemia genes carried by both parents): 5.2% (7/135); all P<0.05], and also higher than the figure in non-monosomy X cases [25.7% (18/70), χ 2=71.55, P<0.001]. In non-monosomy X cases, the detection rates of TS among cases with high-risk results from serological screening for Down's syndrome and NIPT for sex chromosome abnormality [54.7% (29/53) and 68.3% (28/41)] were higher than those of the other two indications [fetal ultrasonographic abnormalities: 25.7% (18/70), other indications: 14.3% (10/70); all P<0.05]. (3) Of the 133 pregnancies with fetal ultrasonographic abnormalities as the indication, 65 (48.9%) had one abnormal ultrasound sign, and 68 (51.1%) had multiple signs. Among the 95 cases with ultrasound abnormalities in the first trimester and 38 cases in the second or third trimester, the incidence of cystic hygroma and hydrops was significantly higher in monosomy X cases than in non-monosomy X cases [in the first trimester: 71.8% (61/85) vs 1/10, 34.1% (29/85) vs 0/10; in the second or third trimester: 73.3% (22/30) vs 0/8, 50.0% (15/30) vs 0/8; Fisher's exact test, all P<0.05]. NT thickness in monosomy X cases was greater than that of non-monosomy X cases [7.5 mm (1.0-17.4 mm) vs 1.7 mm (0.8-9.5 mm), Z=－5.25, P<0.001]. (4) Among the 72 pregnancies with indications other than ultrasound abnormalities, 68 underwent Down's syndrome screening and 61 underwent NIPT. The detection rates among the cases with positive results in Down's syndrome screening, NIPT for a sex chromosome abnormality, and other indications (advanced maternal age, adverse pregnancy history, and thalassemia genes carried by both parents) were 54.4% (37/68), 59.0% (36/61) and 22.2% (16/72), respectively ( χ 2=22.40, P<0.001). The detection rates of the cases with high-risk results from Down's syndrome screening and NIPT for sex chromosome abnormality were higher than that of the cases with other indications ( χ 2=18.77 and 15.40, both P<0.001). Of the 72 pregnancies, 19 (26.4%) were monosomy X and 53 (73.6%) were non-monosomy X, including 42 (58.3%) with chromosomal mosaicism. (5) Among the 205 cases of TS, 185 were successfully followed up (123 were monosomy X and 62 were non-monosomy X). There was one live birth in monosomy X cases (0.8%, 1/123) and 17 in non-monosomy X cases (27.4%, 17/62), and the difference was statistically significant ( χ2=33.22, P<0.001). Sixty-three TS cases with normal ultrasound findings were followed up (18 were monosomy X and 45 were non-monosomy X). In these cases, all 18 pregnancies with monosomy X and 32 (71.1%, 32/45) with non-monosomy X were terminated and the other 13 (28.9%, 13/45) cases of non-monosomy X were delivered. Of the 18 live births, one (non-monosomy X) was delivered at 36 weeks of gestation and the rest were born at term. Eleven cases of them were followed up. The height of one child with monosomy X was lower than the average height of children of the same age and sex by more than 2 standard deviations (－2 SD). The height of 10 children with non-monosomy X were between－1 SD and +3 SD among the children of the same age and gender. The mental and motor development were good in the 11 cases, and no other structural abnormalities were observed. The remaining seven cases refused to be followed up. Conclusions:Ultrasonographic abnormalities are the main indications of fetal TS with monosomy X, while positive Down's syndrome screening and positive NIPT for sex chromosome abnormality are indicators of non-monosomy X. The termination rate for pregnancies with monosomy X is higher than that for non-monosomy X.

Alteraciones citogenéticas en pacientes con diagnóstico de infertilidad en Lima, Perú / Cytogenetic abnormalities in patients with infertility diagnosis in Lima, Peru

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.

Efficacy of second-line therapy with dasatinib in the treatment of chronic myeloid leukemia / 中国基层医药

Objective:To investigate the clinical efficacy of second-line therapy with dasatinib in the treatment of chronic myeloid leukemia.Methods:Sixty patients with chronic phase chronic myeloid leukemia who received treatment in Hongqi Hospital of Mudanjiang Medical University between January 2015 and January 2021 were included in this study. They were randomly divided into control and observation groups, with 30 patients in each group. The control group was treated with conventional chemotherapy, and the observation group was treated with conventional chemotherapy combined with oral dasatinib. All patients were treated for 6 months. Clinical efficacy, immune function indexes, quality of life score, and incidence of adverse reactions (abnormal liver function, rash, fatigue, peripheral edema, nausea and vomiting, alopecia) were compared between the two groups.Results:Objective response rate (ORR) in the observation group was significantly higher than that in the control group [83.33% (25/30) vs. 53.33% (16/30), χ2 = 6.23, P < 0.05). Before treatment, there were no significant difference in immune function indicators between the two groups ( t = 0.03, 0.20, 0.44, all P > 0.05). After treatment, CD 4/CD 8, CD 3+ and natural killer cells in the observation group were (1.03 ± 0.32), (43.77 ± 6.62)%, (31.12 ± 3.38)%, respectively, which were significantly higher than (0.74 ± 0.28), (35.79 ± 6.27)%, (28.22 ± 2.84)% in the control group ( t = 3.69, 4.78, 3.60, all P < 0.05). The scores of social functioning, material well-being life, mental health, somatic health in the observation group were (85.48 ± 6.25) points, (80.12 ± 6.34) points, (79.94 ± 6.48) points, and (77.92 ± 5.81) points, respectively, which were significantly higher than (72.79 ± 5.89) points, (63.47 ± 5.82) points, (68.87 ± 6.08) points, (63.14 ± 6.12) points in the control group ( t = 7.91, 10.59, 6.82, 9.59, all P < 0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group [16.67% (5/30) vs. 40.00% (12/30), χ2 = 4.02, P < 0.05). Conclusion:Second-line therapy with dasatinib for chronic phase chronic myeloid leukemia is effective and safe. It can effectively improve the efficacy and safety of chemotherapy and can also improve immunological function and quality of life.

Changing the molecular profile of primary and metastatic breast cancer identified by Foundation One: case report

Objective: To describe a case report of a patient who presented with bilateral breast cancer with progression to metastatic disease, in which immunohistochemical profile of the primary and metastatic tumor was divergent. Methods: This was a study with a descriptive narrative and reflective design, of the case report type, based on secondary data, with information and images obtained from the electronic medical records of the MVSoul system used in the oncology center of a private hospital in the Federal District in Brazil. Data collection was derived from the analysis of data and images of the electronic medical record. Case report: A patient presented with bilateral metastatic breast cancer, and the primary and metastatic breast tumors showed a difference in immunohistochemical profile. Accordingly, we highlight the rarity of the case, the need for biopsies of metastatic lesions because of the molecular heterogeneity of breast cancer and possible discrepancy between the primary tumor and metastases. Spreading knowledge about diagnostic tests and personalized treatment according to tumor molecular characteristics is also essential, especially when the patient does not have a satisfactory therapeutic response, as in the reported case, since the patient had metastases with different molecular profiles confirmed only by of tumor DNA sequencing.

Caracterización de pacientes con enfermedades genéticas / Characterization of Patients with Genetic Diseases

Introducción: Las enfermedades genéticas se corresponden con variaciones genéticas del desarrollo que precisan ayuda médica, educativa, social o combinaciones de estas. Objetivo: Caracterizar clínica y epidemiológicamente a los pacientes con enfermedades genéticas. Método: Estudio descriptivo transversal. El universo estuvo constituido por los 521 pacientes evaluados en la consulta de asesoramiento genético del municipio Mayarí y la muestra estuvo representada por los 216 pacientes portadores de enfermedades genéticas pertenecientes al Policlínico Universitario 26 de Julio; del Área de Salud de Mayarí, durante el año 2018. Resultados: Predominó el sexo femenino (53,24 por ciento), el grupo de edades de 41 a 50 años (18,06 por ciento), las enfermedades monogénicas (58,8 por ciento), los pacientes con síndrome de Down (20,37 por ciento), los pacientes que no cuentan con antecedentes familiares (54,63por ciento). Conclusiones: Prevalecieron los pacientes con discapacidad mental, con diagnóstico posnatal y con más de 20 años de diagnóstico. El mayor número no realizaba tratamiento. Los pacientes vinculados integralmente a la sociedad resultaron minoría, así como los que tenían antecedentes familiares de enfermedad genética(AU)

Introduction: Genetic diseases are due to developmental genetic variations that require medical, educational and social help, or combinations of these. Objective: To characterize, clinically and epidemiologically, patients with genetic diseases. Method: Descriptive and cross-sectional study. The universe was made up of the 521 patients assessed in the genetic counseling consultation of Mayarí Municipality and the sample was represented by the 216 patients with genetic diseases belonging to 26 de Julio University Polyclinic of the health area of Mayarí, during the year 2018. Results: The female sex predominated (53.24 percent), together with the age group 41-50 years (18.06 percent), monogenic diseases (58.8 percent), patients with Down syndrome (20.37 percent), and patients with no family history of diseases (54.63 percent). Conclusions: Patients with mental disabilities, with postnatal diagnosis and with more than twenty years of diagnosis prevailed. The largest number did not undergo treatment. Patients fully linked to society were a minority, as well as those with a family history of genetic disease(AU)

Grupos de riesgo citogenético de leucemia mieloide aguda pediátrica a partir del análisis de supervivencia en un hospital de referencia para cáncer en Perú / Cytogenetic risk groups for childhood acute myeloid leukemia based on survival analysis in a cancer referral hospital from Perú

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).

Diagnóstico citogenético en una paciente afectada por discapacidad intelectual. Estado Portuguesa, Venezuela / Cytogenetic diagnosis in a patient affected by intellectual disability in Portuguesa State, Venezuela

RESUMEN Introducción: las alteraciones cromosómicas tanto de número como de estructura, son causa importante de morbilidad y mortalidad. Afectan a aproximadamente uno de cada doscientos recién nacidos vivos, siendo la principal causa de discapacidad intelectual. Objetivo: describir el diagnóstico citogenético en una paciente afectada con discapacidad intelectual. Presentación del caso: infante de seis años de edad que es llevado a consulta de asesoramiento genético por presentar discapacidad intelectual, dismorfias y baja talla. Se realiza historia clínica genética, se aplica método clínico y diagnóstico citogenético. Se utilizó bandeo cromosómico GTG y se analizaron 25 metafases. Se realiza cariotipo donde se diagnostica una aberración cromosómica estructural (translocación compleja) en 25 metafases estudiadas, se evidencia la presencia de cuatro cromosomas autosómicos involucrados y los puntos de ruptura: 46,XX, t(7;10;14;18)(p22;q11.1;q31;q11.1). Conclusiones: el estudio permitió ofrecer un diagnóstico, definir el riesgo de recurrencia en la descendencia y mejorar el tratamiento. Se demostró la importancia del asesoramiento genético como herramienta en el nivel primario de salud.

ABSTRACT Introduction: chromosomal alterations both in number and structure are an important cause of morbidity and mortality. They affect approximately one out of every two-hundred live newborns, being the main cause of intellectual disability. Objective: to describe the cytogenetic diagnosis in a patient affected with intellectual disability. Case report: a 6-year-old child who was taken for genetic counseling due to intellectual disability, dysmorphias and short small height. Genetic clinical history was taken; clinical method and cytogenetic diagnosis were applied; GTG chromosome banding was applied and 25 metaphases were analyzed. A structural chromosomal aberration (complex translocation) was diagnosed in 25 metaphases studied, showing the presence of four (4) autosomal chromosomes involved and the breakpoints: 46,XX, t(7;10;14;18)(p22;q11.1;q31;q11.1). Conclusions: the study made possible to provide a diagnosis, define the risk of recurrence in the offspring and improve treatment, supporting the importance of genetic counseling which is a significant tool at primary health care level.

Association of trisomy 21 with anorectal malformation: a cytogenetic study

Background: Anorectal malformations (ARM) are congenital malformations of digestive system resulting from the disturbed development of hindgut during embryogenesis. ARMs involve both sexes; can occur either isolated or in association with other congenital abnormalities and may be associated with chromosomal abnormalities. Association of trisomy 21 with anorectal malformation is well documented. Present study was conducted to assess prevalence of association of trisomy 21 in patients with anorectal malformation.Methods: Total 48 children with diagnosis of anorectal malformation, who were admitted in Department of Paediatric Surgery, King George’s Medical University, Lucknow, Uttar Pradesh, were selected for the study. Blood samples were collected and their cytogenetic analysis was carried out in the Cytogenetics laboratory, Department of Anatomy, KGMU-U.P, Lucknow, India.Results: Among the 48 study subjects, karyogram could be successfully obtained for 45 cases (93.75%). Numerical anomalies were observed in 8.9% cases. Trisomy 21 was found in 6.7%. The prevalence of trisomy 21 was found to more in males (4.5%) as compared to females (2.2%). Prevalence was highest in birth order 3(20%), followed by birth order 2(7.14%) and lowest in birth order 1(3.85%). Trisomy in association with ARM; was observed in children born to females aged >30 years. It was found unrelated to the history of consanguinity.Conclusions: Prevalence of association of trisomy 21 with ARM was found to be 6.7%. This coexistence emphasizes the need for a thorough investigation of patients with ARM.

The correlation between micronuclei count and smoking behavior: a hospital-based study / Correlación entre recuento de micronúcleos y hábito tabáquico: un estudio hospitalario

Background: Micronucleus is a microscopically visible cyto-plasmic chromatin mass in the extranuclear vicinity, originating from aberrant mitosis, which consists of eccentric chromosomes that have failed to reach spindle poles during mitosis. The present study was designed to evaluate and compare cytogenetic changes in the buccal mucosa of smokers and non-smokers based on the occurrence of micronuclei. The study aimed to determine the correlation between the micronuclei count and the frequency and duration of smoking habit. Materials and Methods: Two groups (smokers and non-smokers) of 34 individuals each were examined. Cytological buccal smears were taken from participants using a moistened wooden spatula and stained with standard Papanicolaou stain. Presence of micronuclei was assessed at 40X magnification using a light microscope and a count per 500 cells was determined. The results of the study were analyzed statistically using Mann-Whitney U test, Spearman's rank correlation coefficient and Student t-test. Result: Smears from smokers showed a significant increase in the total number of micronuclei per 500 cell count compared to non-smokers. There was a strong positive correlation between the occurrence of micronuclei and the frequency and duration of smoking. A age-related increase in older age groups was also observed. Conclusion: The study reveals a strong positive correlation between the occurrence of micronuclei and the frequency and duration of smoking. This observation is vital in the utilization of the micronuclei detection in smears as a prognostic, educational and interventional tool in the management of patients with smoking habits.

Antecedentes: El micronúcleo es una masa de cromatina citoplasmática microscópicamente visible en el área extranuclear, que se origina a partir de la mitosis aberrante, y que consiste en cromosomas excéntricos que no han podido alcanzar los polos del huso durante la mitosis. El presente estudio fue diseñado para evaluar y comparar los cambios citogenéticos en la mucosa bucal de fumadores y no fumadores en función de la aparición de micronúcleos. El estudio tuvo como objetivo determinar la correlación entre el recuento de micronúcleos y la frecuencia y duración del hábito de fumar. Materiales and Métodos: Se examinaron dos grupos (fumadores y no fumadores) de 34 individuos cada uno. Se tomaron frotis bucales citológicos de todos los participantes con una espátula de madera humedecida y se tiñeron con la tinción estándar de Papanicolaou. La presencia de micronúcleos se evaluó al microscopio óptico con un aumento de 40X y se determinó un recuento por 500 células. Los resultados del estudio se analizaron estadísticamente utilizando la prueba U de Mann-Whitney, el coeficiente de correlación de rango de Spearman y la prueba t de Student. Resultados: Los frotis de fumadores mostraron un aumento significativo en el número total de micronúcleos por 500 células en comparación con los no fumadores. Hubo una fuerte correlación positiva entre la aparición de micronúcleos y la frecuencia y duración del tabaquismo. También se observó un aumento relacionado con la edad en los grupos de mayor edad. Conclusión: el estudio revela una fuerte correlación positiva entre la aparición de micronúcleos y la frecuencia y duración del tabaquismo. Esta observación es vital en la utilización de la detección de micronúcleos en frotis como una herramienta pronostica, educativa e intervencionista en el manejo de pacientes con hábitos de fumar.

Diagnóstico prenatal citogenético en Cienfuegos: años 2007-2018 / Prenatal Cytogenetic Diagnosis in Cienfuegos: Years 2007-2018

RESUMEN Fundamento: el diagnóstico prenatal citogenético forma parte de la atención que se brinda a la embarazada de alto riesgo y es un componente indispensable de los programas preventivos de genética que impulsa la Organización Mundial de la Salud. Objetivo: exponer los resultados del diagnóstico prenatal citogenético en la provincia Cienfuegos entre los años 2007 y 2018. Método: se realizó un estudio descriptivo, retrospectivo, análisis estadístico y de serie cronológica desarrollado en el Centro Provincial de Genética Médica de Cienfuegos acerca de todos los diagnósticos prenatales citogenéticos que se realizaron entre los años 2007 y 2018. Se analizaron: causas de estudio, cantidad de diagnósticos realizados, tipos de anomalías detectadas, relación entre las causas del estudio con los resultados del diagnóstico. Estos diagnósticos se obtuvieron de la base de datos del laboratorio de la Institución y se realizó una valoración cualitativa y cuantitativa de su comportamiento en el periodo analizado. Los resultados se presentan en tablas mediante números absolutos y porcentajes. Resultados: en el período estudiado se determinaron 3260 diagnósticos prenatales citogenéticos, de ellos 83 presentaron alteraciones cromosómicas, para un 2,6 % de positividad. Solo el 33, 7 % de los casos positivos y sanos portadores tienen menos de 37 años. La anomalía cromosómica más frecuente fue la trisomía libre del 21 (45,8 %), las aberraciones estructurales fueron el 21,7 %, los mosaicos el 13,3 %, y el motivo de indicación más frecuente entre los casos positivos fue la edad materna avanzada (45 casos). Conclusiones: los indicadores analizados se comportan de manera similar a los reportados en en el 2012 y en la literatura de Cuba y del mundo.

ABSTRACT Background cytogenetic prenatal diagnosis is part of the care provided to the high-risk pregnant woman and is an indispensable component of preventive genetic programs promoted by the World Health Organization. Objective: to expose the results of the cytogenetic prenatal diagnosis in the Cienfuegos province between 2007 and 2018. Method: a descriptive, retrospective, statistical and chronological series analysis was carried out at the Provincial Center of Medical Genetics of Cienfuegos about all the cytogenetic prenatal diagnoses made between 2007 and 2018. There were analyzed: causes of study, number of diagnoses made, types of anomalies detected, relationship between causes of the study with the results of the diagnosis. Diagnoses were obtained from the database of the Institution's laboratory and a qualitative and quantitative assessment of their behavior was carried out during the period analyzed. The results are presented in tables using absolute numbers and percentages. Results: 3260 cytogenetic prenatal diagnoses were determined during the study period, 83 of them presented chromosomal alterations, for 2,6 % positivity. Only 33,7 % of positive cases and healthy carriers are under 37 years old. The most frequent chromosomal abnormality was the free trisomy of 21 (45,8 %), the structural aberrations were 21,7 %, the mosaics were 13,3 %, and the most frequent reason for indication among the positive cases was age advanced maternal (45 cases). Conclusions: the indicators analyzed behave similarly to those reported in 2012, in the literature of Cuba and the world.

Cytogenetic Analysis of Down Syndrome Patients in Eastern Uttar Pradesh.

Introduction: Down syndrome (DS) or trisomy 21 is the mostcommon type of chromosomal abnormalities in new-born.There are three types regular (Free) Trisomy 21, Translocationand Mosaic Trisomy 21. One third cases of Down syndrome,clinical diagnosis may not be confirmed. Therefore, in thisstudy we aimed to confirm the suspected Down syndromepatients by a cytogenetic analysis and also evaluate the riskfactors associated with Down syndrome.Material and methods: Total 30 suspected Down syndromepatients with aged between days 2 to 20 years old wereincluded in this study, on the basis of well-defined inclusioncriteria. The cytogenetic analysis, karyotype was carriedout for all 30 suspected patients from peripheral blood andstaining with Giemsa (G-Banding).Results: Total of 30 children were included in which 16patients with Down syndrome and 14 with normal. Regular(Free) Trisomy 21 was found in 93.75% patients andtranslocation was seen in 6.25% case. Whereas Mosaicdown syndrome was not seen in any cases. Among Downsyndrome, 10 (62.50%) were males. The mean maternal ageat birth was significantly higher (31.94±3.04 years) in DownsyndromeConclusion: Our results suggest that regular trisomy 21 ismore common in Down syndrome cases. Moreover, highermaternal age was the major risk factor for Down’s syndrome

Cytogenetic abnormalities, WHO classification, and evolution of children and adolescents with acute myeloid leukemia

ABSTRACT Objectives: To describe cytogenetic and molecular abnormalities observed in children and adolescents with acute myeloid leukemia (AML), classify AML according to the World Health Organization (WHO) classifications from 2008 and 2016, and evaluate the prognosis according to clinical characteristics and cytogenetic abnormalities. Methods: A retrospective longitudinal study was performed on a population of 98 patients with AML, aged up to 16 years, seen in a single hospital from 2004 to 2015. Results: Among the 80 patients for whom it was possible to analyze the karyotype, 78.7% had chromosomal changes, the most frequent being t(15;17)(q22;q21). Of the 86 patients for whom we had cytogenetic or molecular data, making it possible to classify their AML according to the WHO classification, 52.3% belonged to the group with recurrent genetic abnormalities, 22% to the "AML not otherwise specified" group, 18.6% to the group with myelodysplasia-related cytogenetic changes, and 7% to the group with Down syndrome-related leukemia. Five-year overall survival (OS) for the whole group was 49.7% ± 5.2%. In the univariate and multivariate analyses, patients with myelodysplasia-related cytogenetic changes (OS 28.1% ± 12.2%) and those with "AML not otherwise specified" (OS 36.1% ± 11.2%) had an unfavorable prognosis when compared to patients with AML with recurrent genetic abnormalities (OS 71% ± 5.8%) and patients with Down syndrome-related AML (OS 83% ± 15.2%, p = 0.011). Conclusions: The results corroborate the importance of cytogenetic abnormalities as a prognostic factor and indicate the need for cooperative and prospective studies to evaluate the applicability of the WHO classification in the pediatric population.

Application of amniotic fluid cell inheritance and re-culture in cases of amniotic fluid with abnormal traits / 中国基层医药

Objective@#To evaluate amniotic fluid cell inheritance and re-culture in cases of amniotic fluid with abnormal traits.@*Methods@#From January 2014 to December 2018, 15 cases of amniotic fluid with abnormal traits in the First Affiliated Hospital of Anhui Medical University were selected in amniocentesis.Amniotic fluid cells were routinely seeded and cultured for 10 days, then subcultured into other culture bottles.The number of cells and karyotyping after harvesting were counted.@*Results@#Seven of 15 cases of amniotic fluid color were slightly darker, 3 cases were pink as water washed meat, and 5 cases were light brown or brown.The average number of cells in original bottles was (2.40±5.87)×105/mL, the average number of cells in inheritance bottles was (2.76±0.64)×106/mL.All 15 samples in the cell inheritance bottles got satisfactory results in cell karyotype analysis.@*Conclusion@#Amniotic fluid cell inheritance and re-culture can increase the number of cells in amniotic fluid cell culture and improve the success rate of karyotyping.

Application of amniotic fluid cell inheritance and re－culture in cases of amniotic fluid with abnormal traits / 中国基层医药

Objective To evaluate amniotic fluid cell inheritance and re －culture in cases of amniotic fluid with abnormal traits.Methods From January 2014 to December 2018,15 cases of amniotic fluid with abnormal traits in the First Affiliated Hospital of Anhui Medical University were selected in amniocentesis .Amniotic fluid cells were routinely seeded and cultured for 10 days,then subcultured into other culture bottles.The number of cells and karyotyping after harvesting were counted.Results Seven of 15 cases of amniotic fluid color were slightly darker ,3 cases were pink as water washed meat ,and 5 cases were light brown or brown.The average number of cells in original bottles was (2.40 ±5.87)×105／mL, the average number of cells in inheritance bottles was (2.76 ±0.64)×106／mL.All 15 samples in the cell inheritance bottles got satisfactory results in cell karyotype analysis .Conclusion Amniotic fluid cell inheritance and re－culture can increase the number of cells in amniotic fluid cell culture and improve the success rate of karyotyping.

Complex karyotype including ring chromosome 11 in a patient with acute myeloid leukemia: case report

ABSTRACT CONTEXT: Complex karyotypes in acute myeloid leukemia (AML) are characterized by an overall low response rate with frequent relapses after clinical treatment. CASE REPORT: Here, we describe the case of a 61-year-old obese female with clinically diagnosed AML who presented a complex karyotype involving an uncommon abnormality: ring chromosome 11. Immunophenotypic analysis confirmed the diagnosis. Classical and molecular cytogenetic analyses, using GTG banding and FISH (fluorescence in situ hybridization), revealed the presence of complex structural rearrangement involving r(11), add(12)(p13), der(5) and der(13). CONCLUSIONS: Molecular cytogenetic analysis is suitable for better identification and characterization of chromosomal rearrangements in AML. Case reports like this, as well as population-based studies, are necessary for understanding the karyotypic changes that occur in humans.

Clinical and cytogenetic characterization of a patient with tetrasomy 18p / Caracterización clínica y citogenética de un paciente con tetrasomía 18p

The 18p tetrasomy is a structural chromosomal abnormality with the presence of an extra isochromosome 18p, caused by a nondisjunction failure during maternal meiosis II. This additional i(18p) occurs in 1 of 180,000 live-born children worldwide, affecting males and females equally. It is characterized by craniofacial dysmorphisms; ears, nose and throat (ENT) abnormalities; musculoskeletal alterations; and global development delay. We aim to present the clinical and cytogenetic findings of a 3-year-10-month-old Latin American male with i(18p), to support the gene dosage effects, comparing his features with the ones reported in literature. This patient was product of the second pregnancy of a 39-year-old woman and the first son of a 49-year-old man. His main clinical features were microcephaly, facial dysmorphism, generalized hypotonia, and developmental delay. A blood sample of the patient was required to perform a GTG-banded karyotype and a fluorescence in situ hybridization (FISH) for chromosome 18 short arm. In addition, an SNP microarray analysis was carried out to detect genomic imbalances. Cytogenetic analysis revealed the presence of a metacentric supernumerary marker chromosome. The FISH study confirmed the origin of the marker chromosome by showing two signals for the 18p subtelomere and an intermediate signal for the 18 centromere. The microarray analysis showed a copy number gain of 18,385 Mb within the 18p.Tetrasomy tends to be a result of de novo events. The presence of the patient's isochromosome could be explained by advanced maternal age as it is known that this factor has high influence in isochromosome formation. Despite that there were no genes associated with the i(18p)'s clinical manifestations, these features are negatively correlated with dosage effects of the entire short arm. Physical and language therapy was recommended to the patient; the family received medical orientation, and awareness in family planning was raised.

La tetrasomía 18p es una anormalidad cromosómica estructural con la presencia de un isocromosoma extra 18p, causado por una no disyunción durante la meiosis materna II. Este adicional i(18p) ocurre en 1 de 180.000 niños nacidos vivos en todo el mundo, y afecta a hombres y mujeres por igual. Se caracteriza por dismorfias craneofaciales; anomalías en oídos, nariz y garganta (ENT); alteraciones musculoesqueléticas y del desarrollo global. Nuestro objetivo es presentar los hallazgos clínicos y citogenéticos de un varón latinoamericano de 3 años y 10 meses de edad con i(18p), para explicar los efectos de dosificación génica, comparando sus características con las reportadas en la literatura. Este paciente es producto del segundo embarazo de una mujer de 39 años y el primer hijo de un hombre de 49 años. Sus principales características clínicas fueron microcefalia, dismorfia facial, hipotonía generalizada y retraso global en el desarrollo. Se requirió una muestra de sangre del paciente para realizar un cariotipo con bandas GTG y una hibridación fluorescente in situ (FISH) para el análisis del brazo corto del cromosoma 18. Además, se llevó a cabo un análisis de microarreglos para detectar desequilibrios genómicos. El análisis citogenético reveló la presencia de un cromosoma supernumerario metacéntrico. Mientras que el estudio FISH confirma el origen del cromosoma marcador al mostrar dos señales para subtelómeros 18p y una señal intermedia para el centrómero 18. El análisis de microarreglos mostró una ganancia en el número de copias de 18,385 Mb dentro de la región 18p.La tetrasomía tiende a ser el resultado de eventos de novo. El isocromosoma del paciente podría explicarse por la edad materna avanzada, ya que se sabe que tiene una gran influencia en su formación. A pesar de que no hay genes asociados con las manifestaciones clínicas de i(18p), estas características están negativamente correlacionadas con los efectos de dosificación de todo el brazo corto. Se le recomendó terapia física y de lenguaje al paciente, la familia recibió orientación médica y se concientiza sobre la planificación familiar.