OBJECTIVE: To investigate the clinical and laboratory characteristics of hematopoietic tumor with t(5;12)(q33;p13). To sum up the similarities and differences of these diseases. METHODS: The chromosome samples were prepared by short-term training of bone marrow cells, and the karyotype analysis was carried out by R or G band. Using PDGFRb dual color fracture rearrangement probe and fluorescence in situ hybridization (FISH) technology to detect the rearrangement of the gene, the immune-typing analysis was performed using flow cytometry. For 7 cases with t(5;12)(q33;p13) patients with hematopathy were retrospectively analyzed. RESULTS: Seven patients were diagnosed with different diagnoses, mainly male. Nuclear type analysis 5 cases of t(5;12)(q33;p13) was of primary abnormality and 2 cases of secondary abnormality. Five of the seven patients were treated and two untreated. Among the treatment patients, two cases were fatal, two case was lost and one case was treated with combined chemotherapy with dasatinib targeted therapy. The treatment process was successful and is still in hospital. CONCLUSION With t (5;12) (q33;p13) blood system tumors are rare and have unique clinical and laboratory characteristics. At the same time, the heterogeneity is obvious, the patients with tyrosine kinase inhibitor combined with chemotherapy have good effect and good prognosis, and the prognosis of chemotherapy alone is poor.
Chromosomes, Human, Pair 12 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Hematologic Neoplasms ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Retrospective Studies ; Translocation, Genetic

OBJECTIVETodelineate the clinical and genetic features of a patient with myeloproliferative neoplasm (MPN) in association with PDGFRA and EVI1 genes rearrangements.

METHODSClinical data of the patient was collected. Conventional cytogenetics, fluorescence in situ hybridization (FISH) and nested PCR were carried out for the patient.

RESULTSThe patient has featured recurrent rash, joint pain, and intermittent fever. Laboratory tests showed hyperleukocytosis and marked eosinophilia. Physical examination revealed splenomegaly. His karyotype was 46,XY,t(3;5)(q26;q15)[6]/46,XY[10]. FISH assay showed that both PDGFRA and EVI1 genes were rearranged. Molecular studies of the mRNA suggested that there was a in-frame fusion between exon 12 of the PDGFRA gene and exon 9 of the FIP1L1 gene. Imatinib was initiated at a dosage of 200 mg, and after 10 months, the signal of the FIP1L1-PDGFRA fusion gene was undetectable in bone marrow sample. However, the expression of EVI1 mRNA was stable, with no significant difference found between the patient and 10 healthy controls.

CONCLUSIONMPN in association with PDGFRA and EVI1 genes rearrangements have unique clinical and genetic features. Genetic testing is helpful for early diagnosis. Imatinib may be effective for the treatment.

Antineoplastic Agents ; therapeutic use ; Base Sequence ; Chromosome Banding ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; DNA-Binding Proteins ; genetics ; Gene Rearrangement ; Humans ; Imatinib Mesylate ; therapeutic use ; In Situ Hybridization, Fluorescence ; Karyotyping ; MDS1 and EVI1 Complex Locus Protein ; Male ; Myeloproliferative Disorders ; drug therapy ; genetics ; Proto-Oncogenes ; genetics ; Receptor, Platelet-Derived Growth Factor alpha ; genetics ; Transcription Factors ; genetics ; Translocation, Genetic ; Treatment Outcome ; Young Adult

OBJECTIVETo screen for genomic copy number variants (CNVs) in a fetus with one sibling affected with Prader-Willi syndrome using single nucleotide polymorphism (SNP) array.

METHODSThe fetus and its parents were subjected to chromosomal karyotyping and SNP array analysis.

RESULTSA 5p15.33 microdeletions was identified in the fetus and its phenotypically normal mother with a size of 344 kb (113 576 to 457 213). The father was normal for both testing. Analysis of literature and CNVs database indicated the above CNV to be variant of unclear significance. The couple decided to continue with the pregnancy and gave birth to a healthy boy at full-term. No abnormalities were found during the follow-up.

CONCLUSIONThis study may provide further data for the phenotype-genotype correlation of 5p15.33 microdeletion, which differs from Cri du Chat syndrome.

Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Male ; Prader-Willi Syndrome ; diagnosis ; embryology ; genetics ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo use combined G-banding and array-comparative genomic hybridization (aCGH) for the prenatal diagnosis of a fetus with 5q35 deletion syndrome.

METHODSChromosomal karotypes of the fetus and parents were analyzed with G-banding analysis. aCGH was performed to detect minor chromosomal structural abnormalities.

RESULTSThe karyotype of the fetus was ascertained as 46, XY, t(5;10)(q35;p13), and the karyotypes of the parents were normal. aCGH has identified a de novo 1.68 Mb deletion at 5q35.2q35.3 and a 1.44 Mb duplication at 10p14p13.

CONCLUSIONaCGH has a higher resolution and greater accuracy for mapping chromosomal aberrations and is a useful supplement for G banding karyptyping analysis.

Adult ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; genetics ; Comparative Genomic Hybridization ; Cri-du-Chat Syndrome ; diagnosis ; embryology ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Karyotyping ; Male ; Prenatal Diagnosis ; Trisomy ; diagnosis ; genetics

OBJECTIVETo investigate the prenatal application of single nucleotide polymorphism array (SNP array) in the identification of 5p deletion syndrome with partial trisomy 11q.

METHODSG-banded karyotyping and SNP array were performed using amniocytes on a fetus with multiple malformations for the identification of chromosome abnormality. Furthermore, karyotyping was carried out on the parental peripheral blood specimens to ascertain the origin of chromosome abnormalities and then fluorescence in situ hybridization (FISH) was also utilized to confirm the results.

RESULTSKaryotype of amniocyte showed 46, XY, der(5) (?::p15 → qter). SNP array revealed a 13.907 Mb deletion at 5p15.33p15.2 (chr5: 113576-14020561), overlapping the region of 5p deletion syndrome, and a 18.254 Mb duplication at 11q23.3 q25 (chr11: 116684627-134938470), overlapping no known syndrome. Karyotype of the parents showed a normal 46,XX in mother and 46,XY,t(5;11)(p15;q23) in father. Three-color metaphase FISH analysis on paternal peripheral blood specimens also confirmed the paternal karyotyping result.

CONCLUSIONSNP array could uncover 5p deletion syndrome with partial trisomy 11q unidentified by G-banded karyotyping and accurately locate the genomic breakpoints, facilitating the mapping of pathogenic critical regions and the identification of candidate genes, also accumulating research data for genotype-phenotype study.

Adult ; Chromosome Banding ; Chromosome Deletion ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Chromosomes, Human, Pair 11 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; methods ; Trisomy ; diagnosis ; genetics

Here we describe a Syrian couple having recurrent pregnancy loss in the first trimester, fetal malformations, and/or neonatal death. The father had a balanced chromosomal translocation t(5;15), an sY125 microdeletion of locus b in the azoospermia factor (AZF) gene, and an MTHFR C677T homozygous polymorphism with normal phenotype. Interestingly, his healthy wife had another MTHFR A1298C homozygous polymorphism. The couple experienced two pregnancy losses and had two stillborn children with severe malformations due to partial trisomy of the short arm of chromosome 5. The couple does not have any living offspring after 10 years of marriage.
Abortion, Habitual ; genetics ; Azoospermia ; genetics ; Chromosome Aberrations ; Chromosomes, Human, Pair 5 ; Female ; Fetal Death ; etiology ; Homozygote ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Genetic ; Pregnancy ; Translocation, Genetic ; Trisomy

OBJECTIVETo diagnose a neonate presenting with multiple dysmorphic features, Cri-du-chat signs and hypoglycemia and to correlate the phenotype with the genotype.

METHODSThe patient was diagnosed with conventional cytogenetics and real-time fluorescence quantitative PCR (QF-PCR). The phenotype was then correlated with the genotype through a review of literature.

RESULTSThe neonate was diagnosed with a partial 13q trisomy (q12 → qter) and partial 5p monosomy (p15 →pter).

CONCLUSIONA rare diagnosis has been established with combined cytogenetic and molecular genetic techniques. QF-PCR has a broad application in genetic diagnosis.

Chromosomes, Human, Pair 13 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Cri-du-Chat Syndrome ; diagnosis ; genetics ; Cytogenetics ; Female ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases ; diagnosis ; genetics ; Male ; Trisomy ; diagnosis ; genetics

OBJECTIVETo determine the origin of chromosomal aberration for a child featuring multiple malformation, and to correlate the genotype with phenotype.

METHODSRoutine G-banding was performed to analyze the karyotype of the patient and her parents, and array comparative genomic hybridization (array CGH) was used for fine mapping of the aberrant region.

RESULTSThe karyotype of the child was ascertained as 46,XY. Array CGH has mapped a 14.21 Mb deletion to 5p15.2p15.33, and a very small 3.67 Mb duplication to 5q35.3. The patient has presented features such as mental retardation, heart defect, low-set ears, hypertelorism and down-slanting palpebral fissures.

CONCLUSIONChromosome 5 copy number variation can cause multiple malformation. In contrast to routine karyotype analysis, array CGH can map aberrant region with much higher resolution and accuracy.

Abnormalities, Multiple ; diagnosis ; genetics ; Chromosome Aberrations ; Chromosomes, Human, Pair 5 ; DNA Copy Number Variations ; Genotype ; Humans ; Infant ; Male ; Phenotype

OBJECTIVETo determine the karyotype of a boy suspected to have Cri du Chat syndrome with severe clinical manifestations, and to assess the recurrence risk for his family.

METHODSHigh-resolution GTG banding was performed to analyze the patient and his parents. Fluorescence in situ hybridization (FISH) with Cri du Chat syndrome region probe as well as subregional probes mapped to 5pter, 5qter, 18pter, 18qter, and whole chromosome painting probe 18 was performed to analyze the patient and his parents. In addition, single nucleotide polymorphism-based arrays (SNP-Array) analysis with Affymetrix GeneChip Genome-wide Human SNP Nsp/Sty 6.0 were also performed to analyze the patient.

RESULTSKaryotype analysis indicated that the patient has carried a terminal deletion in 5p. FISH with Cri du Chat syndrome region probe confirmed that D5S23 and D5S721 loci are deleted. SNP-Array has detected a 15 Mb deletion at 5p and a 2 Mb duplication at 18p. FISH with 5p subtelomeric probes and 18p subtelomeric probe further confirmed that the derivative chromosome 5 has derived from a translocation between 5p and 18p, which has given rise to a 46,XY,der(5)t(5;18)(p15.1;p11.31)dn karyotype.

CONCLUSIONA de novo 5p partial deletion in conjunction with a cryptic 18p duplication has been detected in a boy featuring Cri-du-Chat syndrome. His parents, both with negative findings, have a low recurrence risk. For its ability to detect chromosomal imbalance, SNP-Array has a great value for counseling of similar patients and assessment of recurrence risks.

Child, Preschool ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 18 ; Chromosomes, Human, Pair 5 ; Cri-du-Chat Syndrome ; diagnosis ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Phenotype ; Polymorphism, Single Nucleotide ; Trisomy

BACKGROUND: Therapy-related myeloid neoplasms (t-MN) occur as late complications of cytotoxic therapy. This study reviewed clinical and cytogenetic characteristics of patients with t-MN at a single institution in Korea. METHODS: The study subjects included 39 consecutive patients diagnosed with t-MN. Each subject's clinical history of previous diseases, treatments, and laboratory data was reviewed, including cytogenetics. The primary diagnosis was hematologic malignancy in 14 patients and solid tumor in 25 patients. RESULTS: Therapy-related acute myeloid leukemia (t-AML, 66.7%) was found to be more common than therapy-related myelodysplastic syndrome (t-MDS). Primary hematologic malignancies that were commonly implicated included mature B-cell neoplasm and acute leukemia. Breast cancer was the most common primary solid tumor. The mean time interval from cytotoxic therapy initiation to t-MN detection was 49 months. Chromosomal aberrations were observed in 35 patients, and loss of chromosome 5, 7, or both accounted for 41% of all cases. Balanced rearrangements occurred in 13 patients; these patients showed shorter latency intervals (mean, 38 months) than patients with loss of chromosome 5 or 7 (mean, 61 months). CONCLUSIONS: In this study, we determined the clinical and cytogenetic characteristics of Korean patients with t-MN. Although our results were generally consistent with those of previous reports, we found that t-MN resulting from de novo leukemia was common and that t-AML was more common than t-MDS at presentation. Multi-institutional studies involving a larger number of patients and additional parameters are required to investigate the epidemiology, genetic predisposition, and survival rate of t-MN in Korea.
Adolescent ; Adult ; Aged ; Antineoplastic Agents/*adverse effects/therapeutic use ; Asian Continental Ancestry Group ; Bone Marrow/pathology ; Breast Neoplasms/drug therapy/pathology/radiotherapy ; Child ; Child, Preschool ; Chromosome Aberrations ; Chromosomes, Human, Pair 5 ; Chromosomes, Human, Pair 7 ; Female ; Hematologic Neoplasms/drug therapy/pathology/radiotherapy ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute/*diagnosis/etiology/genetics ; Male ; Middle Aged ; Myelodysplastic Syndromes/*diagnosis/etiology/genetics ; Neoplasms, Second Primary/*diagnosis/etiology/genetics ; Republic of Korea ; Young Adult