Prenatal Diagnosis of Aberrant Right Subclavian Artery: Association with Genetic Abnormalities / Diagnóstico pré-natal de artéria subclávia direita anômala: associação com anormalidades genéticas

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.

De novo Philadelphia chromosome positive myelodysplastic syndrome: Report of two cases with brief literature review

Myelodysplastic syndromes (MDSs) are characteristically defined by the presence of specific karyotypic abnormalities, based on which they have been prognosticated. Translocation t(9;22)(q34;q11.2) (Philadelphia positive [Ph +ve]) and corresponding BCR-ABL fusion transcript is the defining parameter of chronic myeloid leukemia. It is also seen in a fair proportion of adult acute lymphoblastic leukemia. Occurrence of a Ph +ve MDS is very uncommon, and that too is seen mostly on progression to higher stage/acute leukemia. Even rarer is the de novo presence of Ph positivity in an MDS. A literature search through PubMed has shown only about forty cases of Ph +ve MDS among which less than half had shown Ph positivity at the time of initial diagnosis. Due to its rarity, this entity has not yet found its space in current WHO 2008 classification and is still under “yet to be validated phase” in current practice of hematological malignancies. The benefit of using a tyrosine kinase inhibitor in such a situation is also debatable. We report here two such cases of de novo Ph +ve MDS, diagnosed in last 1½ year at our institute along with brief literature review

Major regulatory mechanisms involved in sperm motility / 亚洲男科学杂志(英文版)

The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies.

Diagnosis and Treatment of Pediatric Acute Myeloid Leukemia / 임상소아혈액종양

Acute myeloid leukemia (AML) is a heterogeneous malignancy that comprises 25-30% of pediatric leukemias in Korea. Several inherited diseases, such as Down syndrome and Fanconi anemia, predispose towards AML leukemogenesis. Subgrouping of AML is a key diagnostic step, previously done with the French-American-British (FAB) classification and recently complemented by that of the World Health Organization (WHO). An important feature of AML is the possibility of chloroma at diagnosis, which, if detected, requires follow-up evaluation to determine treatment response. Numerous genetic abnormalities with prognostic relevance have recently been found, the most important of which include those of the core-binding factor (CBF) leukemias, and FLT3-ITD mutation. These genetic abnormalities, combined with patient response to initial treatment, allow for a scheme of risk stratification, and the current consensus is to treat low risk patients with chemotherapy only, whereas high risk patients may receive allogeneic transplant in first remission, although the benefits of transplant remain inconclusive. Overall, the outcome of children and adolescents with AML has improved significantly so that many clinical trials now report event-free survival of around 60%. However, much of this improvement stems from better supportive care and transplant methods, and the genetics-based diagnostic advances in AML have yet to result in enhanced treatment. New therapeutics, including possibly targeted therapy, are necessary to further improve the outcome of pediatric AML.

Diagnosis and Treatment of Pediatric Acute Myeloid Leukemia / 임상소아혈액종양

Acute myeloid leukemia (AML) is a heterogeneous malignancy that comprises 25-30% of pediatric leukemias in Korea. Several inherited diseases, such as Down syndrome and Fanconi anemia, predispose towards AML leukemogenesis. Subgrouping of AML is a key diagnostic step, previously done with the French-American-British (FAB) classification and recently complemented by that of the World Health Organization (WHO). An important feature of AML is the possibility of chloroma at diagnosis, which, if detected, requires follow-up evaluation to determine treatment response. Numerous genetic abnormalities with prognostic relevance have recently been found, the most important of which include those of the core-binding factor (CBF) leukemias, and FLT3-ITD mutation. These genetic abnormalities, combined with patient response to initial treatment, allow for a scheme of risk stratification, and the current consensus is to treat low risk patients with chemotherapy only, whereas high risk patients may receive allogeneic transplant in first remission, although the benefits of transplant remain inconclusive. Overall, the outcome of children and adolescents with AML has improved significantly so that many clinical trials now report event-free survival of around 60%. However, much of this improvement stems from better supportive care and transplant methods, and the genetics-based diagnostic advances in AML have yet to result in enhanced treatment. New therapeutics, including possibly targeted therapy, are necessary to further improve the outcome of pediatric AML.

Preliminary study on the occurrence of pten and PIK3CA gene mutations in endometrial cancer among Malaysian women

Genetic mutations in endometrial cancer (EC) have been extensively studied in the Western population but not much in Asian cohorts. This study has demonstrated that PTEN and PIK3CA mutations are commonly found in EC among Malaysian women. Following RNA extraction from 20 cancerous and 18 non-cancerous tissues, the presence of mutations in 9 exons of PTEN and 3 exons of PIK3CA genes were detected using realtime PCR, accompanied by High Resolution Melt (HRM) analysis. Sequencing confirmed specificity of each PCR product. The mutations for both genes were detected in the samples with varying frequencies. Notably, all samples expressed mutation of PTEN at exon 7 but none in exon 4. Further analysis demonstrated that strong concurrent mutations occurred between exons 7 of PTEN with exon 20 region 1 of PIK3CA gene (90%). Our data showed mutations are present in EC and not the non-cancerous tissues. Larger samples are being collected to validate this observation.

Asymptomatic pneumatosis intestinalis following chemotherapy for B lymphoblastic leukemia with recurrent genetic abnormalities in an adolescent patient / 대한혈액학회지

Pneumatosis intestinalis (PI) is a rare condition characterized by multiple pneumocysts in the submucosa or subserosa of the bowel. Here, we report a rare case of asymptomatic PI after chemotherapy induction in an 18-yr-old man with B lymphoblastic leukemia with recurrent genetic abnormalities. The patient was treated conservatively and recovered without complications. The possibility of PI should be considered as a complication during or after chemotherapy for hematologic malignancies. Conservative treatment should be considered unless there are complications, including peritonitis, bowel perforation, and severe sepsis.

Diagnóstico y prevención de enfermedades genéticas. Análisis de seis años del municipio Sandino / Diagnostic and prevention of the genetic diseases. Analysis of six years of the municipality Sandino

Introducción: En los últimos años ha aumentado la importancia de las anomalías congénitas y enfermedades hereditarias como causa de muerte en el primer año de vida. El Programa de Diagnóstico y Prevención de Enfermedades Genéticas ha contribuido a la reducción de las tasas de mortalidad infantil, los indicadores de morbilidad mejorar la calidad de vida en la comunidad. Objetivos: Realizar el análisis del comportamiento del Programa de genética médica en el municipio Sandino durante seis años de funcionamiento. Método: Se realizó un estudio descriptivo, prospectivo, de corte longitudinal del total de gestantes desde el 1 de enero de 2000 hasta el 31 de diciembre de 2005, en las dos Áreas de Salud del municipio utilizando datos de la consulta municipal y provincial de Genética. Resultados: 2388 gestantes asistieron a Consulta Genética Comunitaria. 725 de ellas (30.4%) se clasificaron con riesgo incrementado. Los principales fueron la edad materna avanzada, embarazo en la adolescencia y los antecedentes familiares. El 9.84% de las Alfafetoproteínas resultaron elevadas, 48.9 % sin causa explicable. 11 pacientes decidieron no realizarse el diagnóstico prenatal citogenético y de los realizados 1 fue positivo. Los 31 casos de malformaciones detectadas decidieron interrumpir el embarazo. Conclusiones: El acercamiento de los Servicios de Genética Médica a la población y el desarrollo de la Genética Comunitaria facilitan la detección de riesgos si los casos son remitidos a tiempo al servicio de Genética. El embarazo en edades extremas conlleva los principales riesgos genéticos presentes en las gestantes estudiadas. Por cada fallecido se realizaron 6,2 interrupciones de embarazos por malformaciones.

Introduction: In the last years Congenital Anomalies and hereditary diseases have gained importance, as a cause of death during the first year of life. The program for the ¨Diagnosis and Prevention of Genetic Diseases¨ has contributed to the reduction of infant mortality rates, and the morbility indicators, and to improve the quality of life within the community. Objective: To analyze how well the Genetic Program has been functioning in Sandino during the last six years. Method: It was held to descriptive, prospective study of longitudinal out with 100% of all pregnant women from January 1st, 2000 up to December 31st, 2005, in two health areas of the municipality, using data found in both the municipal and the provincial community Genetics Medical Assistance. Results: 2,388 pregnant women were attended in the community's Genetics Assistance, out of them just 725 (30, 4) were detected with increased risk. The main causes were advanced maternal age, teenage pregnancy and family records. Around 9.84% Alpha-fetoproteins reached high levels, 48.9% without a reasonable cause. Eleven patients decided not to go though the cytogenetic prenatal diagnosis and one resulted positive out of those carried out. The 31 cases of malformations detected decided to interrupt their pregnancy. Conclusion: The approach of the Genetic Service in the population y the Community's Genetics assistance contribute to the detection of risks as long as they go to visit the Genetic Physician on time. Pregnancy in deadline age constitutes the main genetic risk present in the pregnant women studied. For each person deceased about 6.2 abortions of pregnancy were done because of malformations.