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.
Chromosomes, Human, Pair 21 ; Humans ; Karyotype ; Karyotyping ; Myelodysplastic Syndromes/genetics* ; Retrospective Studies

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.
Chromosome Deletion ; Chromosome Disorders/genetics* ; Chromosomes, Human, Pair 21/genetics* ; Chromosomes, Human, Pair 22/genetics* ; Female ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; Sequence Deletion/genetics*

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.
Chromosome Banding ; Chromosomes, Human, Pair 21 ; genetics ; DNA Copy Number Variations ; Diagnostic Errors ; Down Syndrome ; Female ; Humans ; Karyotyping ; Trisomy ; diagnosis

Objective: To analyze the characteristics of myeloid neoplasms with t (3;21) (q26;q22) . Methods: Clinical data of patients with t (3; 21) (q26; q22) , diagnosed as hematologic malignancies in Peking University people's hospital from January 2011 to March 2018, were collected retrospectively. 19 patients in our hospital and forty-eight patients bearing t (3;21) (q26;q22) with detailed survival data reported in literature were summarized. Kaplan- Meier method was used for survival analysis. Results: Among 19 patients, including 15 males and 4 females with a median age of 36 years (22-68 years) , 4 cases was diagnosed as de novo acute myeloid leukemia (AML) , 4 as myelodysplastic syndromes (MDS) , 3 as MDS-AML and 8 as chronic myelogenous leukemia (CML) in myeloid blast transformation. All of the 19 patients were detected to have t (3;21) (q26;q22) by G-banding technique and 13 carried additional cytogenetic aberrations. 9 of the 19 patients were detected for positive AML1-MDS1 fusion genes. In the 9 patients with detailed follow-up data, 6 patients received chemotherapy and only 2 achieved complete remission (CR) while 4 with no response. During the follow-up period, 8 patients died and the median overall survival (OS) was 6 months (4.5 to 22 months) . Survival analysis of the present 9 patients together with the literature data showed that the prognosis was poor and the median OS was 7 months. In particular, AML/t-AML had the worst prognosis. Hematopoietic stem cell transplantation (HSCT) could significantly improve survival, the median OS in HSCT group and non-HSCT group were 20.9 and 4.7 months respectively (P<0.001) . Conclusions: t (3; 21) (q26; q22) is a rare recurrent chromosomal abnormality which is detected mainly in myeloid neoplasm and confer to poor clinical prognosis. HSCT should be recommended to improve the outcomes.
Adult ; Aged ; Chromosomes, Human, Pair 21 ; Chromosomes, Human, Pair 3 ; Female ; Humans ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Myeloproliferative Disorders ; Retrospective Studies ; Translocation, Genetic ; Young Adult

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.
Anemia, Aplastic ; Blood Platelets ; Chromosomes, Human, Pair 21 ; Down Syndrome* ; Erythrocytes ; Hemorrhage ; Humans ; Leukemia, Myeloid, Acute ; Leukocytes ; Life Expectancy ; Myeloproliferative Disorders ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Quality of Life ; Wilms Tumor

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.
Chromosomes, Human, Pair 21 ; Down Syndrome* ; Drug Therapy ; GATA1 Transcription Factor ; Hepatomegaly ; Humans ; Infant ; Infant, Newborn* ; Leukemia ; Leukocytosis ; Mosaicism ; Myeloproliferative Disorders* ; Trisomy*

OBJECTIVETo investigate the genetic cause and prognosis of a fetus with a rare karyotype.

METHODSFluorescence 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.

RESULTSThe 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.

CONCLUSIONFISH 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.

Abortion, Eugenic ; Adult ; Chromosome Banding ; Chromosome Deletion ; Chromosome Disorders ; diagnosis ; genetics ; Chromosome Duplication ; Chromosomes, Human, Pair 21 ; genetics ; Chromosomes, Human, Pair 4 ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genetic Counseling ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; methods

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.
B-Lymphocytes* ; Child ; Chromosomes, Human, Pair 21* ; Cytogenetics ; Disease-Free Survival ; Fluorescence ; Humans ; In Situ Hybridization ; Incidence ; Leukocyte Count ; Multivariate Analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Prognosis ; Recurrence ; Survival Rate

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.
Aging ; genetics ; Chromosomes, Human, Pair 21 ; genetics ; Down Syndrome ; genetics ; Female ; Humans ; Maternal Age ; Oocytes ; metabolism ; Polymorphism, Single Nucleotide ; genetics

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.
Adolescent ; Asian Continental Ancestry Group/*genetics ; B-Lymphocytes/*metabolism ; Child ; Child, Preschool ; *Chromosomes, Human, Pair 21 ; Core Binding Factor Alpha 2 Subunit/genetics ; DNA Probes/metabolism ; Female ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Infant ; Infant, Newborn ; Male ; Multiplex Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/genetics ; Proto-Oncogene Proteins c-ets/genetics ; Repressor Proteins/genetics ; Republic of Korea ; Translocation, Genetic ; Young Adult