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

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

No abstract available.
Adult ; Amino Acid Sequence ; Bone Marrow/metabolism/pathology ; Chromosomes, Human, Pair 21 ; Chromosomes, Human, Pair 8 ; Core Binding Factor Alpha 2 Subunit/*genetics ; Exons ; Female ; Humans ; INDEL Mutation ; Leukemia, Myeloid, Acute/*genetics/pathology ; Multiplex Polymerase Chain Reaction ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins c-kit/*genetics ; Transcription Factors/*genetics ; *Translocation, Genetic

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

OBJECTIVETo 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).

METHODSPolymorphisms 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.

RESULTSThe 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.

CONCLUSIONThe 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.

Adult ; Asian Continental Ancestry Group ; ethnology ; genetics ; Case-Control Studies ; China ; Chromosomes, Human, Pair 18 ; genetics ; Chromosomes, Human, Pair 21 ; genetics ; Down Syndrome ; ethnology ; genetics ; Female ; Ferredoxin-NADP Reductase ; genetics ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Single Nucleotide ; Trisomy ; genetics ; Trisomy 18 Syndrome ; Young Adult

Child ; Chromosomes, Human, Pair 21 ; Core Binding Factor Alpha 2 Subunit ; genetics ; Gene Amplification ; Gene Deletion ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Proto-Oncogene Proteins c-ets ; genetics ; Repressor Proteins ; genetics

No abstract available.
*Aneuploidy ; Bone Marrow/pathology ; Chromosomes, Human, Pair 21 ; Down Syndrome/*complications ; Female ; Humans ; Hyperplasia/pathology ; In Situ Hybridization, Fluorescence ; Infant ; Isochromosomes/*genetics ; Karyotype ; Leukemia, Megakaryoblastic, Acute/complications/*diagnosis ; Megakaryocytes/pathology