Clinical Characteristics of Myelodysplastic Syndrome with Patients Chromosome 21 Karyotype Abnormality / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics of myelodysplastic syndrome (MDS) patients with chromosome 21 karyotype abnormality.@*METHODS@#The clinical data of 155 patients with MDS were retrospectively analyzed, the clinical characteristics, survival and factors affecting prognosis of chromosome 21 karyotype abnormality patients were analyzed.@*RESULTS@#Among 155 MDS patients, 4 were 5q- syndrome, 41 were MDS-EB-I, 35 were MDS-EB-II, 27 were MDS-SLD, 46 were MDS-MLD, 1 was MDS-RS-SLD, and 1 was MDS-U. The median follow-up time was 11.0(0.1-120.9) months. Among 155 MDS patients, 13 (9.0%) showed chromosome 21 abnormalities. Among the 13 patients with chromosome 21 karyotype abnormalities, there were 5 cases with simple +21 karyotype, 1 case with del (21q12), 1 case with +8, +21, 1 case with i(21q), 1 case with 20q-, +21, and 4 cases with complex karyotype involving chromosome 21; including 2 cases of MDS-SLD, 4 cases of MDS-MLD, 5 cases of MDS-EB-I and 2 cases of MDS-EB-II. The median survival time of the patients was 3.1 (0.1-6.7) months.@*CONCLUSION@#Chromosome 21 karyotype abnormality is rare in MDS, and the prognosis is worse than the patients without chromosome 21 abnormalities.

Aspectos genómicos, transcriptómicos y del diagnóstico en el síndrome de Down / Genomic, transcriptomic, and diagnostic features of Down syndrome

El síndrome de Down es causado por la presencia de una tercera copia del cromosoma 21 y fue descrito por primera vez en 1838 por Jean-Etienne-Dominique, y más tarde por John Langdon Haydon Down en 1866, mientras trabajaba como superintendente médico en el Asilo Real de Earlswood. Desde ese momento, la comunidad científica puso grandes esfuerzos en tratar de elucidar diversos aspectos que influyen en la naturaleza de esta condición, y que determinan su incidencia y factores de riesgo. De igual manera, se ha puesto interés en los genes involucrados en esta enfermedad, la relación genotipo-fenotipo, la expresión del fenotipo, la variabilidad del material genético y las consecuencias transcripcionales que se producen al tener una tercera copia, ya sea parcial o total, del cromosoma 21. Además, se han invertido esfuerzos en identificar biomarcadores y en diseñar metodologías de diagnóstico prenatal no invasivo que sean altamente eficientes para un mejor diagnóstico del síndrome de Down, y así reducir su impacto negativo en las madres gestantes, al proveerlas de información neutral y precisa acerca de vivir con un hijo con síndrome de Down, y darles autonomía en la decisión de la continuación de su embarazo

Down syndrome is caused by the presence of a third copy of chromosome 21 and was first described by Jean-Etienne-Dominique in 1838, and later by John Langdon Haydon Down in 1866, while working as a medical superintendent in the Royal Earlswood Asylum. Since, the scientific community has placed great efforts in trying to elucidate different influencing features in the nature of this condition that determine their incidence and risk factors. In addition, especial attention has been given to the genes involved in this disease, the genotype-phenotype relationship, the expression of the phenotype, the variability of the genetic material and the transcriptional consequences that are produced by having a third copy, either partial or total, of chromosome 21. Additionally, efforts have been invested in identifying biomarkers and designing noninvasive prenatal methodologies that are highly efficient for a better diagnosis of Down syndrome, in order to reduce its negative impact in pregnant mothers, by providing them with neutral and accurate information about life with a child with Down syndrome, as well as providing the autonomy in the decision to continue their pregnancy

Prenatal diagnosis of a fetus with Phelan-McDermid syndrome and 21q21 microdeletion by multiple genetic techniques / 中华医学遗传学杂志

OBJECTIVE@#To carry out prenatal diagnose for a fetus with ultrasonography abnormalities using multiple genetic techniques.@*METHODS@#Routine G-banding chromosomal analysis and single nucleotide polymorphism array (SNP-array) were applied in conjunction for the prenatal diagnosis of the fetus. The result was confirmed by fluorescence in situ hybridization (FISH).@*RESULTS@#SNP-array detected that the fetus has carried a hemizygous 5.1 Mb deletion at 22q13.31q13.33, which is associated with Phelan-McDermid syndrome, and a hemizygous 4.5 Mb deletion at 21q21.1q21.2. FISH analysis of the fetus and its parents suggested that both deletions were de novo in origin.@*CONCLUSION@#The hemizygous deletions on 21q21.1q21.2 and 22q13.31q13.33 probably underlay the abnormal phenotype of the fetus. Genetic analysis can provide crucial information for the prenatal diagnosis and genetic counseling.

Reflection of a case misdiagnosed as trisomy 21 syndrome by G-banded chromosomal karyotyping analysis / 中华医学遗传学杂志

OBJECTIVE@#To emphasize the clinical significance of copy number variations (CNVs) detection by describing a case misdiagnosed as trisomy 21 syndrome by G-banded chromosomal karyotype analysis.@*METHODS@#A girl with obesity and short stature was diagnosed as trisomy 21 syndrome by G-banded chromosomal karyotype analysis. Considering the discrepancy of her karyotype with her phenotype, genomic CNVs was detected by next-generation sequencing and the result was verified by quantitative PCR (qPCR).@*RESULTS@#A microduplication of 16p11.2: 29 642 339-29 775 631 (133.292 kb) was detected. qPCR assay for QPRT and SPN located in the duplicated region confirmed the finding of CNVs assay. Meanwhile, her parents did not present similar duplication in 16p11.2.@*CONCLUSION@#The 16p11.2 microduplication was a novel genomic structural variation in the girl, though it may not be associated with her clinical manifestations. Chromosomal microarray or next-generation sequencing-based CNVs detection can accurately determine the origin of small supernumerary marker chromosome and reduce the chance of misdiagnosis.

A Case of Transient Myeloproliferative Disorder Associated with Clonal Trisomy 21 in a Chromosomally Normal Newborn / 임상소아혈액종양

Transient myeloproliferative disorder (TMD) is similar to congenital leukemia, with leukocytosis, increased peripheral blast cells, and hepatomegaly in the neonatal period. Although TMD occurs only in patients with Down syndrome and trisomy 21 mosaicism, there have been reports of congenital leukemia with trisomy 21 limited to hematopoietic cells showing spontaneous resolution. We identified trisomy 21 in the leukemic cells in a patient with congenital leukemia. As there was no other gene abnormality, we stopped chemotherapy, and the disease resolved spontaneously. We reviewed the cases of clonal trisomy 21 TMD and found that their clinical features were similar to those of TDM associated with Down syndrome. In conclusion, in a phenotypically normal patient with suspected congenital leukemia, it is necessary to confirm the presence of 21 trisomy. If the neonate has only trisomy 21 without other gene abnormalities, intensive chemotherapy may not be required.

A Concomitant Hemato-Oncologic Disorder of Patient with Down Syndrome

A patient with Down syndrome has hematologic and oncologic disorders of medical complication. Down syndrome shows that characteristic hematologic and oncologic abnormalities and developments of disorders are different at ages. Many hematologic disorders were related to Down syndrome. There are diseases of red blood cells, white blood cell disorders, platelet and bleeding disorders, aplastic anemia, and transient myeloproliferative disease. Acute myeloid leukemia, acute lymphoblastic leukemia, and rarely solid tumors (Neuroblastoma, Wilm's tumor, Hodgkin's lymphoma) are also associated with Down syndrome. We checked clinical manifestations of each disorder and we should make standard hematologic index of different age groups. In addition, the relations between chromosome 21 and hemato-oncologic disorders should be found. We need to investigate potential therapeutic interventions that can improve quality of life and life expectancy in patients with Down syndrome.

Anormalidades genéticas e de metilação de DNA em uma coorte de leucemia linfoblástica aguda pediátrica com alterações no cromossomo 21 / Genetic and DNA methylation abnormalities in a cohort of acute lymphoblasticleukemia with chromosome 21 alterations

A leucemia linfoblástica aguda de células precursoras B (LLA-CPB) é uma neoplasia heterogênea. Aproximadamente 60% das LLA-CPB apresentam alterações envolvendo o cromossomo 21, incluindo hiperdiploidia, fusão gênica ETV6‐UNX1 e amplificação intracromossomal do cromossomo 21 (iAMP21). Mecanismos epigenéticos contribuem para a leucemogênese e a metilação do DNA, por sua vez, pode ser modulada por polimorfismos na via do folato. Portanto, este estudo tem como objetivo caracterizar o perfil genético e de metilação de DNA em LLA-CPB com alterações no cromossomo 21. Este estudo partiu de uma série de 1006 casos de LLA-CPB diagnosticados de 2002-2016 e foi desenhado em 3fases: 1) Identificação dos casos com alterações em número de cópias (CNA) no cromossomo 21 usando multiplex ligation probe amplification (MLPA) e FISH (RUNX1 e sondas para os cromossomos 4, 8, 10, 14, 17, 18, X e Y); 2) Caracterização do perfil de metilação e CNA por meio da técnica de microarranjo. Para tanto, o DNA foi modificado com EZ DNA Methylation™ Kit e o perfil de metilação analisado pelo Infinium Human Methylation 450 BeadChip Kit; e 3) Análises comparativas de metilação de DNA gene-específica, metilação em LINE-1(pirosequenciamento) e genotipagem para o polimorfismo MTHFR rs1801133 (PCR-RFLP) entre os diferentes subtipos moleculares de LLA-CPB, controles e amostras em remissão. Encontramos evidências de ganhos em CNA no cromossomo 21 em 83/374 (22%) das amostras (MLPA)...

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous disease. Approximately 60% of BCP-ALL present alterations involving chromosome 21 (chr 21), including high hyperdiploid, ETV6‐RUNX1 fusion and intrachromosomal amplification of thechromosome 21 (iAMP21). Contributing with this process, epigenetic mechanisms could regulate the transcription and induce leukemogenesis. Polymorphisms in genes involved in folate metabolism could influence this aberrant methylation. This study aimed to characterize the genetic and DNA methylation profile of BCP-ALL with chr 21 aberrations, as well as to identify the DNA methylation signatures of different BCP-ALL molecular subgroups. This study enrolled 1006 BCP-ALL diagnosed between 2002-2016 and was performed in tree steps: 1) Identification of copy number alterations (CNA) regarding the Chr 21 by multiplex ligation probe amplification (MLPA) and FISH (“LPH012 TEL/AML1 translocation, dual fusion probe and centromere probes to chr 4, 8, 10, 14, 17, 18, X and Y); 2) DNA methylation and CNAcharacterization by DNA methylation array. DNA from BCP-ALL cases, controls and remission samples was modified with EZ DNA Methylation™ Kit and analyzed by the InfiniumHumanMethylation450 BeadChip Kit; 3) Comparative gene methylation, LINE-1 methylation (pyrosequencing) and MTHFR rs1801133 genotype (PCR-RFLP) analysis between the different BCP-ALL subgroups. We found evidence of gains in chr 21 in 83/374 (22%) of the samples analyzed by MLPA. Among the BCP-ALL with chr 21 gains, 11/83 (13%) had ≥5 RUNX1 signals and 53/83 (64%) were classified as hyperdiploid...

Prenatal diagnosis of a case with 46,XX,del(4),dup(21) / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the genetic cause and prognosis of a fetus with a rare karyotype.</p><p><b>METHODS</b>Fluorescence in situ hybridization (FISH) was used for verifying a structural chromosomal abnormality detected by conventional karyotyping analysis. Whole genome DNA microarray was used to analyze copy number variations carried by the fetus.</p><p><b>RESULTS</b>The fetus was found to have a 46,XX,dup(21)(?q21q22) karyotype, which was verified by FISH analysis as repetition of chromosome 21 region, namely nuc ish 21q22×3. Whole genome DNA microarray confirmed that there was a 17.87 Mb duplication in the 21q21.3q22.3 region, which involved GATA1, JAK2 and ALL genes and spanned the Down syndrome region. The genes are implicated in craniofacial abnormalities, cardiac abnormalities, mental retardation, growth retardation, limb abnormalities. In addition, there was also an 8.43 Mb deletion in the 4p16.1p16.3 region, which involved FGFR3, LETM1, WHSC1 and WHSC2 and other 64 OMIM genes and spanned the Wolf-Hirschhorn syndrome region. The genes are implicated in growth retardation, craniofacial abnormalities, cardiac abnormalities, mental retardation, and hypotonia. After consultation, the family chose to terminate the pregnancy at 25th week of gestation.</p><p><b>CONCLUSION</b>FISH can help to verify structural chromosome abnormalities suspected by conventional karyotyping analysis. Combined with whole genome microarray, these can determine copy number variation and its region containing the disease genes, and facilitate clinical analysis of the fetus.</p>

Intrachromosomal amplification of chromosome 21 in Korean pediatric patients with B-cell precursor acute lymphoblastic leukemia in a single institution

BACKGROUND: Intrachromosomal amplification of chromosome 21 (iAMP21), defined as the presence of three or more RUNX1 signals on one marker chromosome, is a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that is known to have a poor prognosis when treated with standard therapy. The aim of this study was to evaluate the clinical characteristics of Korean children with iAMP21. METHODS: The cytogenetic data from BCP-ALL children were reviewed. The ETV6/RUNX1 ES Dual Color Probe was used for fluorescence in situ hybridization (FISH). RESULTS: In total, 295 children were included. Of these, 10 patients (3.4%) had iAMP21. The median age of iAMP21 patients was 9 years, and the median value of white blood cell count was 5.09×10⁹/L. Slow early treatment response was observed more in iAMP21 patients. Patients with iAMP21 had a higher incidence of relapse and worse survival rates. In patients with iAMP21, the estimated 10-year cumulative incidence of relapse was 53.3%. The estimated 10-year event-free survival and overall survival rate were 46.7% and 64.8%, respectively. Most cases of leukemic relapse developed in the late period (median, 43 mo). In multivariate analysis, high risk group was the only factor that had a significant impact on death. CONCLUSION: The existence of iAMP21 was related to delayed treatment response and was likely to affect increased relapse and death in the late period. Further studies are needed to reveal its effect on BCP-ALL treatment outcomes and its role as an independent prognostic factor.

Advances of research on the mechanism of Down syndrome birth at advanced maternal age / 中华医学遗传学杂志

Down syndrome is caused by partial or complete triplication of genes located on chromosome 21. Its incidence increases dramatically with the age of women. Hypotheses proposed for this have included abnormal homologous recombination, defective spindle assembly, biological aging, reduction of cohesion complexes, endocrine disorders, oocyte selection model, and single nucleotide polymorphisms of genes that maintain chromosome stability, etc. A literature review is provided here.

A Novel KIT INDEL Mutation in Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1

No abstract available.

Frequency and Clinical Characteristics of Intrachromosomal Amplification of Chromosome 21 in Korean Childhood B-lineage Acute Lymphoblastic Leukemia

BACKGROUND: Intrachromosomal amplification of chromosome 21 (iAMP21) is known to be associated with poor prognosis in B-cell ALL (B-ALL). To determine the frequency and clinical characteristics of iAMP21 in Korean B-ALL patients, we performed FISH and multiplex ligation-dependent probe amplification (MLPA) analyses. METHODS: A total of 102 childhood B-ALL patients were screened with ETV6-RUNX1 FISH probes (Abbott Molecular, USA). The presence of an iAMP21 was confirmed by using MLPA P327 iAMP21-ERG probemix (MRC Holland, The Netherlands). RESULTS: iAMP21 was detected in one of the screened B-ALL patients (1/102 patients, 1.0%) who presented the ALL immunophenotype and complex karyotype at initial diagnosis. The patient relapsed twice after bone marrow transplantation. MLPA showed 12.5-Mb and 4.28-Mb regions of amplification and deletion, respectively. CONCLUSIONS: The frequency of iAMP21 is considerable in Korean pediatric patients. Our report suggests that iAMP21 in childhood B-ALL has very unfavorable impact on patient's prognosis. Additional methods such as MLPA analysis is essential to rule out patients with equivocal interphase FISH results.

Trastornos neurológicos graves y malformaciones en una niña con monosomía del cromosoma 21 / Severe neurological disorders and malformations in a girl with mo- nosomía of the chromosome 21

Se presenta el caso de una niña de 7 años de edad, que fue remitida a la Consulta de Asesoramiento Genético, por presentar malformaciones congénitas severas y rasgos dismórficos, asociado a un retardo del neurodesarrollo. Al nacer se diagnosticó una comunicación interauricular, lo cual fue corregido mediante operación cardiaca. Se le realizó estudio por técnicas de citogenética convencional obteniéndose como resultado una monosomía del cromosoma 21. El estudio de citogenética molecular por técnica FISH detectó una inserción de la zona crítica del 21 en la región subtelomérica del 6p.

The case of a 7-year-old girl is showed. She was referral to the Genetic Advice Session, for presenting severe congenital malformations and dysmorphisms, associated with a neurological delay. A canal inter auricle was diagnosed at birth, which was corrected through heart surgery. The conventional cytogenetic analyzed showed a 21 chromosome monosomy. The study of molecular cytogenetic detected an insertion of the critical region of 21 in the subteloméric 6p region.

Association of MTHFR and MTRR genes polymorphisms with non-disjunctions of chromosomes 18 and 21 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the effect of MTHFR and MTRR genes polymorphisms on chromosomes 18 and 21 non-disjunction through investigation of Henan Han Chinese young females with a gestational history of trisomy 21 (Down syndrome, DS) or trisomy 18 (Edwards syndrome, ES).</p><p><b>METHODS</b>Polymorphisms of MTHFR 677C/T, MTHFR 1298A/C and MTRR 66A/G were analyzed in 73 healthy females (controls group), 78 females with a gestational history of DS (DS group) and 54 females with a gestational history of ES (ES group) by direct sequencing of PCR products from amplification of peripheral blood lymphocyte DNA.</p><p><b>RESULTS</b>The frequency of MTHFR 677T allele was significantly different among the DS group, ES group and the control group (P<0.05). The frequency of MTRR 66G allele was significantly different only between the DS group and the control group (P<0.05). MTHFR 1298A/C polymorphisms were not associated with either ES or DS. Compared with the wild genotype MTHFR 677CC or MTRR 66AA, carriers of the MTHFR 677CT, 677TT, or MTRR 66GG genotypes had respectively 2.694 times (95%CI: 1.204-6.025, P<0.05), 5.451 times (95%CI: 2.211-13.435, P<0.05) and 9.618 times (95%CI: 2.085-44.365, P<0.05) risk of bearing a DS baby. Compared with the wild genotype MTHFR 677CC, carriers of the MTHFR 677CT and 677TT genotype had respectively 2.701 times (95%CI: 1.133-6.438, P<0.05) and 3.804 times (95%CI: 1.406-10.293, P<0.05) risk of bearing a ES baby. Neither MTRR 66AG or 66GG genotype was associated with the occurrence of ES.</p><p><b>CONCLUSION</b>The MTHFR 677T and MTRR 66G may represent a risk factor for DS gestation, while MTHFR 677T may represent a risk factor for ES gestation for Chinese Han females.</p>

Clinical features and survival analysis of patients with CD56 expression in de- novo acute myeloid leukemia with t（8;21） / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical features and survival of patients with CD56 expression in de- novo acute myeloid leukemia（AML）with t（8;21). .</p><p><b>METHODS</b>Clinical data of 82 de novo AML with t（8;21）who were newly diagnosed from Jan 2008 to Apr 2014 were analyzed retrospectively, 50 expressed CD56 and 32 not. Clinical characteristics and prognoses were compared between patients expressing and nonexpressing CD56.</p><p><b>RESULTS</b>There were no statistically significant differences in terms of age, gender, white blood cell count（WBC）, percentage of bone marrow blasts, extramedullary infiltration rate, the early mortality or the presence of additional cytogenetic abnormalities between CD56 + and CD56- groups（P＞0.05). The expressions of lymphatic antigens CD19 between CD56 + and CD56- groups showed significant difference （30.0% vs 53.1% , P=0.036). The complete remission and 3-year overall survival（OS）showed no significant differences between CD56+ and CD56-groups, while 3- year disease- free survival（DFS）showed significant differences（25.8% vs 46.9%, P=0.014). Multivariable analysis for DFS identified CD56 positivity as an independent predictor. DFS of who received allogeneic hematopoietic stem cell transplantation（HSCT）was better than those treated with intermediate- dose cytarabine/high dose cytarabine（IDAC）as postremission therapy.</p><p><b>CONCLUSION</b>The expression of CD56 in de-novo AML with t（8;21) appeared to be associated with poorer prognosis.</p>

Application of next-generation DNA sequencing for prenatal testing of fetal chromosomal aneuploidies / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies.</p><p><b>METHODS</b>Plasma from 4004 women with singleton pregnancy at a gestational age between 12-35(+5) weeks was collected prior to amniocentesis between April 19th 2011 and December 31st 2013. The samples were divided into three groups: (1) High risk for Down syndrome by biochemical screening; (2) Advanced maternal age; (3) Abnormalities by ultrasound or other methods. Plasma DNA extracted from above samples was sequenced at low coverage. Positive results were verified against the karyotypes of the fetuses. For those with negative results, the fetuses were followed up by telephone call for at least six months after birth.</p><p><b>RESULTS</b>Among 4003 samples subjected to non-invasive prenatal diagnosis, 66 (1.65%) had a positive result. In group 1, 22 cases of trisomy 21 (T21), 3 cases of trisomy 18 (T18), 1 case of 13 trisomy (T13), 8 cases of 45,X and 2 cases of other chromosomal abnormality were detected. In group 2, 13 cases of T21, 2 cases of T18, 1 case of T13, 5 cases of 45,X, 2 cases of 47,XXN and 1 case of other chromosomal abnormality were detected. In group 3, 1 case of T21, 1 case of T18, 1 case of T13, and 3 cases of 47,XXN were detected. For 55 samples underwent prenatal diagnosis, 30 cases of T21 and 4 cases of T18 were discovered, which was consistent with the results of non-invasive prenatal diagnosis. For the 13 cases indicated as 45,X, 3 were verified by karyotype analysis, 2 were verified as mosaicism (45,X/46,XN), 8 were 46,XN (false positives). For the 5 cases indicated as 47,XXN, 2 were verified by karyotype analysis, the other 3 were 46,XN (false positives). Karyotypes of 3 cases suspected for other chromosomal abnormalities were all verified as 46,XN (false positive). Until May 1st 2014, telephone follow-up for those with negative screening results only identified a boy with facial abnormalities and developmental delay, which was similar to his older sister, combined karyotyping and fluorescence in situ hybridization analysis has verified the karyotype of the boy as 46,XY,rec(14)dup(14q)inv(14)(p12q14)pat.</p><p><b>CONCLUSION</b>Our results indicated that sequencing of plasma free DNA can rapidly detect fetal chromosomal aneuploidies. The method is non-invasive, and the results are highly consistent with karyotype analysis in terms of accuracy and specificity. Non-invasive testing can be used as an effective adjunct to conventional prenatal diagnostic methods, which can greatly reduce unnecessary invasive prenatal diagnosis. However, the sensitivity and accuracy for aneuploidy detection other than chromosome 13/18/21 still need to be improved.</p>

Prognostic impact of loss of sex chromosomes in children with acute myeloid leukemia subtype M2 / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the relationship between loss of sex chromosomes and prognosis in children with acute myeloid leukemia (AML) M2 subtype.</p><p><b>METHODS</b>According to cytogenetic characteristics, 106 children with AML were divided into three groups: patients with normal karyotype (Group A, n=26), patients with abnormal karyotype who had no loss of sex chromosomes (Group B, n=52), and patients with abnormal karyotype who had loss of sex chromosomes (Group C, n=28). Prognosis was compared between the three groups.</p><p><b>RESULTS</b>The 5-year event-free survival (EFS) rates of Groups A, B, and C were (38.9±11.2)%, (59.3±7.3)%, and (66.5±10.5)%, respectively; the EFS of Group C was significantly higher than that of Group A (P=0.035). The 5-year overall survival (OS) rates of Groups A, B, and C were (54.3±13.5)%, (68.1±7.7)%, and (77.9±9.8)%, respectively (P>0.05). The 5-year EFS of 58 patients with t(8;21) was (63.3±7.3)%, significantly higher than that of patients with normal karyotype (P=0.015). All the 28 cases in Group C had t(8;21), and their 5-year EFS was not significantly different from that of patients with t(8;21) in Group B (P>0.05).</p><p><b>CONCLUSIONS</b>Loss of sex chromosomes is a favorable karyotype in children with AML M2 subtype and the patients in this group mostly have t(8;21). Why loss of sex chromosomes indicates a favorable prognosis is probably because it is accompanied by t(8;21) in the patients.</p>

A Case of Pentasomy 21 With Two Isochromosome 21s in Acute Megakaryoblastic Leukemia Associated With Down Syndrome

No abstract available.

Utilidad diagnóstica del examen molecular de los genes PPA, PSEN-1 y PSEN-2 en Enfermedad de Alzheimer de inicio temprano / Diagnostic utility of the molecular examination of the genes PPA, PSEN-1 and PSEN-2 in early onset Alzheimer's disease

INTRODUCCIÓN: la enfermedad de Alzheimer (EA) es una enfermedad neurodegenerativa de evolución progresiva que representa el tipo más común de demencia. El riesgo de presentar enfermedad de Alzheimer familiar (EAF) puede aumentar 2 a 4 veces entre los individuos que tienen un familiar de primer grado con la enfermedad, para la cual se han identificado mutaciones en tres genes, definidas como causales (PSEN-1, PSEN-2 y APP). OBJETIVO: evaluar la utilidad del estudio molecular de los genes PSEN-1, PPA, PSEN-2 (cromosomas 14, 21 y 1) en el diagnóstico de enfermedad de Alzheimer de inicio temprano (EAIT). METODOLOGÍA: se realizó una búsqueda de evidencia en las bases de datos: MEDLINE, EMBASE, la Librería Cochrane y LILACS. Dos evaluadores de manera independiente, tamizaron las referencias obtenidas, resolviendo las discrepancias por consenso. Se identificaron únicamente estudios descriptivos, a partir de los cuales se basan los resultados del presente informe. RESULTADOS: se identificaron 5 estudios descriptivos. Los estudios confirman la identificación de los 3 genes determinantes en la aparición de la enfermedad de EAIT; las mutaciones más frecuentemente identificadas son las pertenecientes al gen PSEN-1. CONCLUSIONES: el estudio molecular de los genes PSEN-1, PSEN-2 y PPA en pacientes con demencia de inicio temprano (< de 65 años) e historia familiar de demencia, se considera el patrón de oro para el diagnóstico de EAIT de transmisión autosómico dominante.(AU)

Prenatal diagnosis of Down syndrome using cell-free fetal DNA in amniotic fluid by quantitative fluorescent polymersase chain reaction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Amniotic fluid (AF) supernatant contains cell-free fetal DNA (cffDNA) fragments. This study attempted to take advantage of cffDNA as a new material for prenatal diagnosis, which could be combined with simple quantitative fluorescent polymerase chain reaction (QF-PCR) to provide an ancillary method for the prenatal diagnosis of trisomy 21 syndrome.</p><p><b>METHODS</b>AF supernatant samples were obtained from 27 women carrying euploid fetuses and 28 women carrying aneuploid fetuses with known cytogenetic karyotypes. Peripheral blood samples of the parents were collected at the same time. Short tandem repeat (STR) fragments on chromosome 21 were amplified by QF-PCR. Fetal condition and the parental source of the extra chromosome could be determined by the STR peaks.</p><p><b>RESULTS</b>The sensitivity of the assay for the aneuploid was 93% (26/28; confidence interval, CI: 77%-98%) and the specificity was 100% (26/26; CI: 88%-100%). The determination rate of the origin of the extra chromosome was 69%. The sensitivity and the specificity of the assay in the euploid were 100% (27/27).</p><p><b>CONCLUSIONS</b>Trisomy 21 can be prenatally diagnosed by the QF-PCR method in AF supernatant. This karyotype analysis method greatly reduces the requirement for the specimen size. It will be a benefit for early amniocentesis and could avoid pregnancy complications. The method may become an ancillary method for prenatal diagnosis of trisomy 21.</p>