Application of copy number variation sequencing in patients with intellectual disability/developmental delay and autistic spectrum disorder / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with intellectual disability (ID), developmental delay (DD), and autistic spectrum disorder (ASD).@*METHODS@#Forty patients with ID/DD/ASD referred to Nanshan Maternity and Child Health Care Hospital from September 2018 to January 2022 were enrolled. G-banded karyotyping analysis was carried out for the patients. Genomic DNA was extracted from peripheral blood samples and subjected to CNV-Seq analysis to detect chromosome copy number variations (CNVs) in such patients. ClinVar, DECIPHER, OMIM and other database were searched for data annotation.@*RESULTS@#Among the 40 patients (including 30 males and 10 females), 16, 15 and 6 were diagnosed with ID, DD and ASD, respectively. One patient had combined symptoms of ID and DD, whilst the remaining two had combined ID and ASD. Four patients were found with abnormal karyotypes, including 47,XY,+mar, 46,XY,inv(8)(p11.2q21.2), 46,XX,del(5)(p14) and 46,XX[76]/46,X,dup(X)(p21.1q12). Chromosome polymorphism was also found in two other patients. CNV-seq analysis has detected 32 CNVs in 20 patients (50.0%, 20/40). Pathogenic CNVs were found in 10 patients (25.0%), 15 CNVs of uncertain clinical significance were found in 12 patients (30.0%), and 7 likely benign CNVs were found in 4 patients (10.0%).@*CONCLUSION@#Chromosome CNVs play an important role in the pathogenesis of ID/DD/ASD. CNV-seq can detect chromosomal abnormalities including microdeletions and microduplications, which could provide a powerful tool for revealing the genetic etiology of ID/DD/ASD patients.

Malformaciones congénitas en óbitos fetales / Congenital malformations in fetal stillbirth

INTRODUCCIÓN. Las malformaciones congénitas son defectos estructurales o funcionales producidos en el desarrollo embrionario o fetal, de diversa etiología, algunas son prevenibles por lo que el diagnóstico prenatal es indispensable para determinar pronóstico y futuro obstétrico. OBJETIVO. Describir las malformaciones congénitas prevalentes en óbitos fetales y destacar la importancia de completar el diagnóstico prenatal. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo y retrospectivo. De una población de 276 Historias Clínicas con diagnóstico de pérdidas fetales espontáneas, se tomó muestra de 41 con malformaciones congénitas del Centro Obstétrico, en el Hospital de Especialidades Carlos Andrade Marín, de enero 2017 a diciembre 2018. Criterios de inclusión: diagnóstico óbitos con malformaciones congénitas menores de 34 semanas de gestación identificadas por estudio ecográfico, cromosómico y de necropsia. Criterios de exclusión: óbitos con estudio de necropsia normal. Los datos se obtuvieron del sistema MIS-AS400. El análisis se realizó con el programa Microsoft Excel. RESULTADOS. Se encontró prevalencia de malformaciones congénitas en óbitos fetales del 14,85% (41; 276), el hidrops representó el 41,46% (17; 41), de estos en el 53% (9; 17) se hallaron malformaciones mayores y en el 47% (8; 17) otras malformaciones asociadas. Se encontraron 17 cariotipos, 76,47% (13; 17) fueron anormales y 23,52% (4; 17) normales. DISCUSIÓN. Las comorbilidades maternas y antecedentes familiares, fueron factores relevantes para la aparición de malformaciones congénitas cuya prevalencia aún se debe investigar en el Ecuador. CONCLUSIÓN. Se describieron malformaciones congénitas prevalentes y la importancia de realizar el control prenatal con estudios complementarios para precisar el diagnóstico y determinar el futuro obstétrico.

INTRODUCTION. Congenital malformations are structural or functional defects produced in embryonic or fetal development, of diverse etiology, some are preventable, so prenatal diagnosis is essential to determine prognosis and obstetric future. OBJECTIVE. Describe the prevalent congenital malformations in stillbirths and highlight the importance of completing the prenatal diagnosis. MATERIALS AND METHODS. Observational, descriptive and retrospective study. From a population of 276 Clinical Histories with a diagnosis of spontaneous fetal losses, a sample of 41 with congenital malformations was taken from the Obstetric Center, at the Carlos Andrade Marín Specialty Hospital, from January 2017 to December 2018. Inclusion criteria: diagnosis of deaths with malformations congenital less than 34 weeks of gestation identified by ultrasound, chromosomal and necropsy study. Exclusion criteria: deaths with normal autopsy study. The data were obtained from the MIS AS400 system. The analysis was carried out with the Microsoft Excel program. RESULTS. The prevalence of congenital malformations in stillbirths was 14,85% (41; 276), hydrops represented 41,46% (17; 41), of these, 53% (9; 17) found major malformations and in 47% (8; 17) other associated malformations. 17 karyotypes were found, 76,47% (13; 17) were abnormal and 23,52% (4; 17) were normal. DISCUSSION. Maternal comorbidities and family history were relevant factors for the appearance of congenital malformations whose prevalence has yet to be investigated in Ecuador. CONCLUSION. Prevalent congenital malformations and the importance of carrying out prenatal control with complementary studies to clarify the diagnosis and determine the obstetric future were described.

Investigation of chromosomal alterations in patients with Alzheimer's disease in the state of Amazonas, Brazil / Investigação de alterações cromossômicas em pacientes com doença de Alzheimer no estado do Amazonas, Brasil

ABSTRACT Alzheimer's disease (AD) has as its main characteristic the deterioration of cerebral functions. Its etiology is still complex and undefined despite the progress made in understanding its neurological, infectious, biochemical, genetic and cytogenetic mechanisms. Considering this, the aim of this study was to investigate the presence of chromosomal alterations in the peripheral blood lymphocytes, and to verify if there was a high frequency of these alterations in patients diagnosed with AD at the University Hospital GetúLio Vargas Outpatient Clinic Araújo Lima in Manaus, Amazonas, Brazil. Among the nine patients in the AD group, only one patient did not have metaphases with chromosomal alterations (2n = 46,XX), while eight patients with AD showed numerical chromosomal alterations, classified as X chromosome aneupLoidy (2n = 45,X) and double aneupLoidy (2n = 44,X,-X,-10; 2n = 44,X,-X,-13 and 2n = 44,X,-X,-21). In the control group, no chromosomal changes were found in the karyotypes of these individuals. Therefore, the karyotypes of patients with AD undergo chromosomal alterations at different levels. These findings are being described for the first time in the population of Amazonas, and they highlight the importance of the inclusion of cytogenetic investigations in the routine management of patients with AD.

RESUMO Doença de Alzheimer (DA) tem como principal característica a deterioração das funções cerebrais. Quanto a sua etiologia ainda é complexa e indefinida, apesar do progresso alcançado na compreensão de seus mecanismos neurológicos, infecciosos, bioquímicos, genéticos e citogenéticos. Considerando isto, nós investigamos a presença de alterações cromossômicas nos Linfócitos de sangue periférico e verificamos se há uma alta frequência dessas alterações em pacientes já diagnosticados com doença de Alzheimer no Hospital Universitário Getulio Vargas / Ambulatório Araújo Lima, Manaus / Amazonas / Brasil. Assim, dos 09 pacientes do grupo DA, somente 01 paciente não apresentou metáfases com alterações cromossômicas (2n = 46,XX) enquanto que 08 pacientes com DA apresentaram alterações cromossômicas numéricas, sendo classificadas como aneupLoidia do cromossomo X (2n = 45,X) e aneupLoidia dupLa (2n = 44,X,-X,-10; 2n = 44,X,-X,-13 e 2n = 44,X,-X,-21). No grupo controle, não foram encontradas aLterações cromossômicas nos cariótipos desses indivíduos. Estes achados para a popuLação do Amazonas/ BrasiL estão sendo descritos pela primeira vez. Os cariótipos de pacientes com DA sofrem aLterações cromossômicas em diferentes níveis e demonstraram a importância das investigações citogenéticas no manejo rotineiro de pacientes com DA.

Les dysgonosomies au laboratoire de cytogénétique et de biologie moléculaire de la faculté des sciences de la santé de Cotonou de 1999 à 2016

Les dysgonosomies sont des anomalies des chromosomes sexuels diagnostiquées sur la base du caryotype. Ce groupe de maladies chromosomiques est peu connu en Afrique sub saharienne à cause du manque d'outils diagnostiques. Dans le but de faire connaitre ce groupe d'affections et d'en faciliter le diagnostic et la prise en charge, une étude rétrospective des cas de dysgonosomies diagnostiqués au Laboratoire de Cytogénétique et de Biologie Moléculaire de la Faculté des Sciences de la Santé de Cotonou a été réalisée. Elle a couvert la période allant de janvier 1999 à septembre 2016 par exploitation des registres du Laboratoire. Les données collectées étaient épidémiologiques, cliniques et cytogénétiques. L'incidence annuelle des dysgonosomies sur la période d'étude (17 ans) était de trois cas par an avec une prévalence de 2,6 % dans ledit laboratoire. L'âge moyen des patients était de 15,16 ans avec un minimum de 02 jours et un maximum de 40 ans. La sex-ratio était de 1,08. Les motifs de demandes de caryotype les plus fréquents étaient les anomalies de développement sexuel (59,61%) et l'infertilité (15,38%). Les principales anomalies chromosomiques retrouvées étaient le syndrome de Klinefelter (n=12), le syndrome de Turner (n=6), un isochromosome du X et un syndrome XXYY. Les dysgonosomies ne sont pas rares dans la population fréquentant le Laboratoire de Cytogénétique et de Biologie Moléculaire de Cotonou et possèdent une variabilité phénotypique

Clinical Utility of a Diagnostic Approach to Detect Genetic Abnormalities in Multiple Myeloma: A Single Institution Experience

BACKGROUND: The identification of genetic abnormalities in patients with multiple myeloma (MM) has gained emphasis because genetics-based risk stratification significantly affects overall survival (OS). We investigated genetic abnormalities using conventional cytogenetics and FISH and analyzed the prognostic significance of the identified additional abnormalities in MM. METHODS: In total, 267 bone marrow samples were collected from February 2006 to November 2013 from patients who were newly diagnosed as having MM in a tertiary-care hospital in Korea. The clinical and laboratory data were retrospectively obtained. Cox proportional hazard regression was used to examine the relationship between clinical/genetic factors and survival outcome, using univariate and multivariate models. RESULTS: Using conventional cytogenetic analysis and FISH, 45% (120/267) and 69% (183/267) patients, respectively, were identified to harbor genetic abnormalities. In the univariate analysis, the following genetic variables were identified to affect OS: abnormal karyotype (P 65 years) (P=0.013) with an HR of 2.505 (95% CI, 1.218–5.151). CONCLUSIONS: Our findings highlight the importance of applying a comprehensive approach for detecting genetic abnormalities, which could be closely associated with the prognostic significance of MM.

Pattern of karyotypic aberrations in pakistani patients with de novo acute myeloid leukemia

Background: Acute myeloid leukemia [AMI] is a malignant disease of the bone marrow in which karyotypic analysis is the most important diagnostic and prognostic tool for predicting remission rate, relapse and overall survival. This study was carried out to determine the frequency and type of cytogenetic aberrations in de novo acute myeloid leukemia in adults at a tertiary care hospital

Materials and methods: This descriptive cross-sectional study was carried out in the Hematology Department, Liaquat National Hospital from November 2014 to April 2016.A total of 51 cases were diagnosed with AMI during the study period. Cytogenetic analysis was carried out by banding technique on bone marrow aspirate samples

Results: The mean age of the study subject was 42.03+/-17.70 years. Frequency of karyotyping abnormalities was observed in 47% of cases, in which most frequently occurring cytogenetic abnormalities were those of good cytogenetics including t[15;17] and t[8;21], seen in 23.5% and 9.8% of cases respectively. Intermediate risk cytogenetics including Del 9q was seen in 1.96% of cases. However, poor risk cytogenetics including complex cytogenetics, t[11;q23] and del [13] were seen in 7.8%, 1.96% and 1.96% of cases respectively. Normal cytogenetics was seen in 27 [52.9%] patients

Conclusion: Karyotyping is one of the most important diagnostic and prognostic tools and a maximum benefit could be attained through cytogenetic analysis. Cytogenetic aberrations in our series are more or less similar as reported at national level with preponderance of good risk cytogenetics in our setting

Chromosome microarray analysis of four fetuses with abnormal karyotypes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To carry out chromosomal microarray analysis (CMA) on four fetuses with abnormal karyotypes.</p><p><b>METHODS</b>Amniotic fluid samples were obtained and subjected to routine G-banded karyotyping analysis. CMA was applied for cultured amniocytes to determine alterations of gene dosage and chromosomal breakpoints.</p><p><b>RESULTS</b>Abnormal karyotypes were found in the parents of 3 fetuses. Parental karyotypes of the remaining fetus were normal. Imbalance chromosome rearrangements were revealed by CMA in all 4 cases.</p><p><b>CONCLUSION</b>CMA is an effective tool for the evaluation of clinical significance and delineation of the breakpoints involved in complex chromosomal rearrangements.</p>

Abnormal Karyotypes Involving 1q21 and 12p13 and Their Clinical Significance / 中国实验血液学杂志

Many hematological malignances involve recurrent chromosomal abnormalities, and the reciprocal translocation is one of them. However, there are a lot of chromosomal abnormalities with lower incidence and unclear clinical significance. Among them, the one abnormal karyotype translocation, t (1;12) (q21; p13) is a rare karyotype change. Only 6 patients had been reported to have this karyotype and all of them suffered from hematologic diseases, including one case of acute myeloid leukemia, one case of high-risk myelodysplastic syndrome, two children with acute lymphoblastic leukemia, one case of chronic myeloid leukemia at accelerated phase and one case of multiple myeloma. Among them, the fusion gene were detectable in two cases. In this article, the common chromoscme karyotype abnormality involving 1q21 and 12p13, and genes involving in these regious are summarized, moreover the reported cases of t(1;12) (q21;p13) are reviewed.

Analysis of Clinical Features and Prognosis in 31 Patients with Primary Myelofibrosis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and laboratorial features of primary myelofibrosis (PMF) patients treated in our hospital, to analyze the risk factors influancing survival, and to compare several prognostic scoring systems.</p><p><b>METHODS</b>parameters about clinical and laboratorial features were taken from medical documents at diagnosis, univariate analysis was conducted by Kaplan-Meier method, the survival data were compared with Log-rank test, and a COX model was used for multivariate analyses.</p><p><b>RESULTS</b>In our center the anemia and JAK2V617F mutation were more common, while the abnormal karyotype was less common, the constitutional symptoms, splenomegaly, Hb level < 100 g/L and LDH are adverse factors for survival in univariate analysis. Constitutional symptoms and Plt count < 100 × 10(9)/L are adverse factors of survival according to multivariate analysis.</p><p><b>CONCLUSION</b>The anemia is more frequent in Chinese patients. Constitutional symptoms and Plt count < 100 × 10(9)/L are independent risk factors for survival. LILLI, modified IPSS, modified DIPSS are suitable to our data.</p>

FLT3 Gene Mutations in Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was aimed to detect the FLT3 gene mutation in patients with de-novo acute myeloid leukemia (AML), and to investigate its prognostic value and clinical significance.</p><p><b>METHODS</b>Polymerase chain reaction (PCR) was used to detect FLT3 gene mutation, in bone marrow samples of 54 patients with de novo AML.</p><p><b>RESULTS</b>The incidence of FLT3-ITD mutation in 54 de-novo AML patients was 22.22%, 10 out of 12(83.3%) AML patients were identified with normal karyotype, while 16.7% patients were identified as with abnormal karyotype. The peripheral blood white cell count and bone marrow blast cells were significantly higher in the patients with FLT3-ITD mutation than those in patients without FLT3-ITD mutation (P<0.05), but there was no statistically significant difference in sex, age, CR rate of the first course induction chemotherapy, survival rate and so on between the two groups. Two cases had FLT3-TKD gene mutation; as compared with FLT3-TKD negative AML patients there was no statistical difference in sex, age, white blood cell count, the percentage of marrow blasts and CR rate of the first course of treatment at the initial diagnosis.</p><p><b>CONCLUSION</b>FLT3-ITD mutation positive likely occurs in AML patients with normal karyotype, the FLT3-ITD mutation is associated with higher peripheral white cell count and higher percentage of bone marrow blast cells.</p>

Prognostic significance of monosomal karyotype in acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the prognostic significance of monosomal karyotype (MK) in patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>The clinical data of 498 AML patients were analyzed retrospectively.</p><p><b>RESULTS</b>Of the 498 patients, 233 (46.8%) cases had an abnormal karyotype. 42 patients fulfilled the criteria for MK, which were 8.4% of all cases and 18.0% of patients with abnormal karyotype, respectively. The most frequent autosomal monosomies were -7 and -17. 70 patients had complex karyotype (CK), in all patients and patients with abnormal karyotype accounted for 14.1% and 30.0%, respectively. Patients with MK were associated with significantly older (median age 62.5 vs 52 years, P=0.003), and lower HGB concentrations (62.5 vs 77 g/L, P=0.009) and lower WBC counts (7.0×10⁹/L vs 11.7×10⁹/L, P=0.008). Among MK cases, the most frequent chromosome abnormalities were complex karyotype, -7, -5, 7q-, and 5q-. In univariate analysis, MK patients had worse survival than those without MK (7.3 months vs 26.3 months, P<0.001). CK patients also had poorer outcomes than patients without CK (14.8 months vs 26.3 months, P<0.001). In CK patients, survival was worse in MK patients than patients without MK (7.4 months vs 19.2 months, P=0.007). By COX analysis, MK was an independent prognostic factor, beyond NCCN criteria and CK [HR=2.610 (1.632-4.175), P<0.001].</p><p><b>CONCLUSION</b>MK was an independent adverse prognostic factor in AML patients.</p>

Analysis of the karyotype abnormalities and its prognostic in 298 patients with myelodysplastic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between cytogenetic markers with World Health Organization (WHO) classification, disease progress and prognosis in cases with primary myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>298 patients with de novo MDS from the first affiliated hospital of medical school, Zhejiang University were enrolled in the retrospective analysis of WHO classification, karyotype, and prognosis. Follow-up study was also conducted.</p><p><b>RESULTS</b>The WHO classifications at first diagnosis were as follows: refractory cytopenia with unilineage dysplasia (RCUD), 18 cases; refractory anemia with ring sideroblasts (RARS), 8 cases; refractory cytopenia with multiline dysplasia (RCMD), 104 cases; refractory anemia with excess blasts-1, 76 cases; refractory anemia with excess blasts-2, 85 cases; MDS unclassified (MDS-U), 5 cases involved; and single del (5q), 2 cases. 39.6% of MDS patients carried karyotypic abnormalities. Among them, the frequency of numerical abnormalities, structural abnormalities and the existence of composite abnormalities were 45, 31, and 42, respectively. The composite abnormalities were unbalanced translocations and complex chromosomal abnormalities. The incidence of both karyotypic abnormalities and complex chromosomal abnormalities in RAEB group was higher than that in non-RAEB group (P<0. 05). An analysis based on IPSS-R Scoring System showed that advanced risk stratification (except the low-risk group) gradually enhanced the incidence of karyotypic abnormalities (P<0.05). In addition, the probability of evolution to leukemia increased with the higher IPSS-R score (P<0.05). In RAEB group, the cases with +8 chromosome, accounting for 19.5% of karyotypic abnormalities, had worse prognosis than those with normal chromosomes.</p><p><b>CONCLUSION</b>Karyotype was identified with an independent risk factor in MDS patients. Therefore, the information on cytogenetic analysis was critical for diagnosis, prognosis and individual treatment. MDS patients presenting+8 chromosome, an intermediate risk factor, were associated with a poorer outcome compared to cases with normal chromosomes in RAEB group.</p>

Clinical and cytogenetic study of chromosome 1 abnormality in myelodysplastic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the incidence of chromosome 1 abnormality in myelodysplastic syndrome（MDS）to couple its association with clinical presentation and prognosis.</p><p><b>METHODS</b>R- band karyotype analyses were performed in 672 cases of MDS between 2010 and 2013. Clinical data of those with abnormal chromosome l were collected and then analyzed factors affecting the prognosis.</p><p><b>RESULTS</b>Of 672 cases of patients with MDS, chromosome 1 aberration［der（1）, dup（1）, －1 were most frequent］ were found in 41（6.1%）cases. 1q trisomy was found in 18/41（43.9%）cases, and the most common patterns were duplication of the long arm as well as unbalanced translocation with other chromosomes. Of 41 patients with chromosomal 1 abnormality, 32 cases were accompanied with other chromosomal aberration, usually involving 3 or more abnormal chromosomal karyotypes, e.g., chromosome 8, 7 abnormalities. According to IPSS-R scoring system, 19 patients were diagnosed with very high risk, 10 patients high risk, 10 patients intermediate risk and 2 patients low risk MDS. 9 patients transformed into acute leukemia with median transforming time of 7.18（0.56-54.28）months. Median survival of 36 cases after 2010 was 17.48（95% CI 14.38-20.58）months. There were significant differences on median survival between RAEB and non-RAEB groups（χ²=10.398, P=0.001）, and between with more than 3 chromosome abnormalities and with less than 3 groups（χ²=3.939, P=0.047）. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.</p><p><b>CONCLUSION</b>Chromosome 1 aberration was not rare in MDS. 1q trisomy was the most common abnormal karyotype in China, which often accompanied with other chromosomal abnormalities. The prognosis of MDS patients with chromosome 1 abnormality was poor, especially worse in those diagnosed with RAEB-1, RAEB-2 and with more than 3 chromosome abnormality. For patients whose percentage of bone marrow blasts less than 5%, the prognosis of patients with 1q trisomy was better than those without 1q trisomy. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.</p>

IDH1 Gene Mutation and Its Clinical Significance in patients with Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the incidence rate of IDH1 in acute myeloid leukemia and analyze its effect on clinical characteristics and prognosis.</p><p><b>METHODS</b>Mononuclear cells in bone marrow samples were collected from 192 adult patients with newly diagnosed AML. Polymerase chain reaction (PCR) and direct sequencing were used to amplify exon 4 of IDH1 gene, the gene sequencing was used to analyze the gene mutations, at same time, the detection of NPM1, FLT3-TKD, FLT3-ITD, C-KIT, CEPBA, TET2 and JAK2V617F and MLL mutations were carried out, the follow-up was used to determine its therapeutic efficacy and outcomes of patients. The clinical and laboratory data of these cases were collected, and their clinical characteristics and prognosis were then analyzed.</p><p><b>RESULTS</b>Among the 192 AML patients, 13 cases were detected with IDH1 gene mutation, the mutation rate was 6.77% [95% CI (5.70%-13.38%)]. The sequencing chart of IDH1 gene showed double peaks, the mutations were heterozygous, out of them c.G395A (p.R132H) was found in 8 cases, c.C394T was found in 4 cases (p.R132C), c.C394A (p.R132S) was found in 1 cases, R132H and R132C are common, 13 cases showed missense mutation. The median age in mutation group was 52 years old, the median age in unnutration group was 40 years, there was significant difference between them (P = 0.010). Mutation rate of IDH1 gene in M1 and M2 was significantly higher than that in other FAB subtypes. There were no significant difference in sex, newly diagnosed peripheral white blood cell count, hemoglobin, platelet count, peripheral blood and bone marrow original cell proportion of primitive cells between them. Mutation of IDH1 gene had certain correlation with NPM1 gene mutation, but no correlation with FLT3-TKD, FLT3-ITD, C-KIT, TET2 and JAK2V617F and MLL natations was found. In addition, the IDH1 mutation easily occurred in patients with normal karyotype or in patients with middle prognostic risk karyotype, IDH1 mutation occurred in 11 cases with normal karyotype, the mutation rate was 10.28%, IDH1 mutation were observed in 2 cases with abnormal karyotype, the mutation rate was 3.50%, there was significant difference. In AML patients with middle prognostic risk karyotype. The complete remission (CR) and the 3 year survival (OS) rate of IDH1 mut patients were less than that in IDH1 wt, there was significant difference (P < 0.05).</p><p><b>CONCLUSIONS</b>The IDH1 mutation more easily occurr in older AML patients and mutations effect of IDH1 on clinical characteristics may represent a molecular marker for poor prognosis in AML.</p>

Prognostic evaluation of comorbidities in patients with myelodysplastic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To discuss the impact of comorbidities on the outcomes of patients with MDS.</p><p><b>METHODS</b>The clinical characteristics of 676 MDS patients with detailed comorbidities evaluations was analyzed retrospectively.</p><p><b>RESULTS</b>There were 395/676 cases (58.4%) with comorbidities (group 1), 281/676 cases (41.6%) without (group 2). Significant differences were seen in the distribution of age (≥ 60 y), bone marrow blasts, abnormal karyotype, WHO 2008 subtypes and IPSS-R risk cohorts (P<0.05) between the two groups. While gender, HGB concentrations, WBC levels, platelet levels and serum ferritin were not significantly different (P>0.05). Independent prognostic significance of comorbidities was seen in both uni-variate and multi-variate analyses (P<0.001). According to MDS-specific comorbidity index (MDS-CI), the median survival were 32(1-153) months, 19(2-85) months and 13(1-37) months in the low-risk, intermediate-risk and high-risk cohorts respectively, while 96(1-166) months in cohorts without any comorbidities, of which significant differences were seen (P<0.001). The MDS-CI allowed further stratification in the IPSS-R low-risk, intermediate-risk and high-risk cohorts (P<0.001).</p><p><b>CONCLUSION</b>Comorbidities provides prognostic stratification independently of IPSS-R for MDS patients.</p>

Avaliação cariotípica de pacientes com clínica de Síndrome de Down no HUAP-UFF / Karyotypic evaluation of patients with down syndrome clinic in HUAP-UFF

O objetivo do presente estudo foi analisar o perfil cariotípico de pacietnes que deram entrada no Hospital Universitário Antonio Pedro-HUAP (Universidade Federal Fluminense), durante o período de 2006 a 2010, com clínica de síndrome de Down (SD) e determinar a ocorrência de cariótipos clássicos, mosaicismos e translocações. Para avaliação do cariótipo foi realizada a técnica de bandeamento G a partir de culturas de linfócitos. Dos 157 pacietnes que tiveram avaliação cariotípica solicitada no Laboratório de Hematologia-HUAP, 39 tinham clínica de SD, sendo que 32 apresentavam trissomia do cromossomo 21, um, translocação 21q:21q e, dois, translocação 14q:21q. Dois casos de mosaicismo foram detectados. Duas amostras não foram diagnosticadas como SD. Além disso, dois foram detectados. Duas amostras não foram diagnosticadas como SD. Além disso, dois casos não associados à suspeita clínica de Síndrome de Down foram diagnosticados como trissomia de cromossomo 21. O diagnóstico preciso da SD é fundamental para a orientação clínica adequada dos indivíduos afetados e para o fornecimento de informações relevantes ao planejamento familiar. O presente estudo indica a ocorrência destas alterações genéticas na população encaminhada ao Laboratório de Hematologia-HUAP, para análise do perfil cariotípico, demonstrando que o diagnóstico laboratorial correto é necessário para confirmar a clínica dos pacientes, salientando a importância da interação clínico laboratorial.

retrospective chromosome studies among Iranian infertile women: report of 21 years

The infertility is an important health problem, affecting about 15% of couples. The important role of genetic factors in pathogenesis of infertility is now increasingly recognized. The value of karyotyping women in the routine work-out of couples referred for sterility has long been recommended. The aim of this study was to define the frequency of all chromosomal aberrations among women which referred to our department due to infertility during the 21-year period. In this 21-year retrospective study, for the first time, we investigated 896 women which referred to our department due to infertility during 1986 to 2006. For chromosome analysis, heparinized peripheral blood samples were cultured, harvested and banded according to standard methods. Out of 896 patients, 710 patients [79.24%] had a normal karyotype, and 186 patients [20.76%] showed abnormal karyotype. Among the abnormal ones 48 patients [25.81%] showed Turner's syndrome [45,X], and 45 patients [24.19%] were sex reversal with 46,XY karyotype. The rest of 93 patients [50%] revealed a wide range of chromosome abnormalities. Our results emphasized the importance of the standard cytogenetic methods in assessing the genetic characteristics of infertile females, which allows detecting a variety of somatic chromosome abnormalities, because some of these may interfere with the success of reproduction

Application and evaluation of invasive prenatal diagnostic techniques and analysis of chromosomal karyotype / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the safety, effectiveness and complications of serial invasive prenatal diagnostic techniques, and to investigate the prenatal diagnosis indication as well as to analyze the abnormal chromosomal karyotype.@*METHODS@#We retrospectively studied all patients from March 2005 to May 2012 who received amniocentesis and cordocentesis in the prenatal diagnosis center of Second Xiangya Hospital. The indication of the procedure, successful rate and complications were evaluated, and 25 abnormal chromosome nuclear types were analyzed.@*RESULTS@#A total of 669 patients received invasive prenatal diagnosis from March 2005 to May 2012 in Second Xiangya Hospital: 598 received amniocentesis and 71 cordocentesis carried out. Compared with the cordocentesis group, the amniocentesis group had higher achievement ratio (91.54% vs 100%, P<0.05), lower spontaneous abortion rate (1.41% vs 0.33%, P<0.05), fewer abnormal karyotypes (11.27% vs 2.84%, P<0.05) and lower expenditure (880 yuan vs 800 yuan, P<0.05). Positive screening, advanced maternal age, and ultrasonography abnormality were the top 3 indications of amniocentesis and cordocentesis. We found 25 abnormal karyotypes, including 6 cases of trisomy 21, 4 sex chromosomal abnormalities, 7 autosomal balanced translocations, 1 marker chromosome, and 7 mosaics.@*CONCLUSION@#As a widely used invasive prenatal diagnosis, amniocentesis is safe and effective. The complications of cordocentesis are much higher than those of amniocentesis, which is not a proper routine procedure for prenatal diagnosis of abnormal karyotype. The analysis of karyotype not only can identify fetal chromosome abnormality, but also provide the scientific basis for pregnancy continuation, thus reducing the ratio of birth defect.

Acute myeloid leukemia with t(11;12)(p15;q13) translocation: two cases report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and laboratory features of acute myeloid leukemia (AML) with t(11;12)(p15;q13) translocation.</p><p><b>METHODS</b>Two cases of AML with t(11;12)(p15;q13) translocation were reported and the related literatures were reviewed.</p><p><b>RESULTS</b>The diagnosis of AML-M3 was supported by morphological, cytochemical staining and electron microscope tests. A rare t(11;12)(p15;q13) translocation, but not classical t(15;17)(q22;q12) translocation and PML- RARα fusion gene, was detected in both cases. Both of the patients were refractory to differentiation induction therapy such as retinoic acid and arsenic trioxide.</p><p><b>CONCLUSION</b>AML is a group of heterogeneous disease derived from hematopoietic stem cell. Cytogenetic characteristic is important for diagnosis, prognosis stratification and therapy selection. Because of the heterogeneity of clinical and molecular features, it is unsuitable to classify AML with t(11;12)(p15;q13) as AML with recurrent cytogenetic aberration. This group of disease may benefit from allogeneic hematopoietic stem cell transplantation.</p>