Background: Abnormal chromosome may be abnormal in number or structure of chromosomes related to normal chromosomes or sex chromosomes. One sign of abnormal chromosomes that we can observe during pregnancy is the abnormal ultrasound images. Objectives: To discover the relations between the chromosomal abnormalities and some fetal abnormalities determined by ultrasound. Subjects and method: A prospective descriptive study combined with a retrospective study on 250 pregnant women with fetal abnormalities from Aug 2006 to Aug 2008. Results: Among 250 pregnant women with fetal abnormalities determined by ultrasound taken amniocentesis, rate of late amniocentesis (over 20 weeks) was the highest (50.8%), while rate of ideal amniocentesis (16-20 weeks) only accounted for 29.6%. Abnormal chromosomal rate of multiple abnormalities of fetus statistically significant were higher than that of mono abnormal of fetus (46.8% vs. 18.5%/ p<0.0l). Conclusion: Abnormal phenotype determined by ultrasound; rate of chromosomal disorder was 27.2%.
chromosomal analysis ; fetal abnormalities

CCCTC-binding factor (CTCF) is a highly conserved zinc finger protein and is best known as a transcription factor. It can function as a transcriptional activator, a repressor or an insulator protein, blocking the communication between enhancers and promoters. CTCF can also recruit other transcription factors while bound to chromatin domain boundaries. The three-dimensional organization of the eukaryotic genome dictates its function, and CTCF serves as one of the core architectural proteins that help establish this organization. The mapping of CTCF-binding sites in diverse species has revealed that the genome is covered with CTCF-binding sites. Here we briefly describe the diverse roles of CTCF that contribute to genome organization and gene expression.
Animals ; Cell Cycle Proteins/metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; *Gene Expression Regulation ; Genome ; Humans ; Protein Binding ; Protein Interaction Maps ; Repressor Proteins/analysis/*metabolism

OBJECTIVETo identify novel binding proteins of hSNF5, a subunit of chromatin remodeling complex in human fetal brain.

METHODSThe yeast two-hybrid system was used for this study. Positive cDNA clones were sequenced. Sequence homology and putative functional domains were analyzed and compared with databank.

RESULTSNine positive clones obtained were analyzed, among which the sequence of one clone was 97% homologous to the 3' mRNA of a hypothetical protein FLJ20643, while other four clones were related to protein coding sequences existed in the GenBank. The rest four clones were not in frame with any known protein coding sequence.

CONCLUSIONSClones encoding for hSNF5 binding protein exists in cDNA library of human brain. These proteins may recruit chromatin remodeling complex via hSNF5 to modulate the transcription of their target gene and the related cell functions.

Brain ; cytology ; metabolism ; Chromosomal Proteins, Non-Histone ; Cloning, Molecular ; DNA, Complementary ; genetics ; DNA-Binding Proteins ; analysis ; genetics ; isolation & purification ; Embryo, Mammalian ; Humans ; SMARCB1 Protein ; Trans-Activators ; Transcription Factors ; analysis ; genetics ; isolation & purification ; Transcription, Genetic ; Two-Hybrid System Techniques

Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous congenital anomaly. Mutations in the NIPBL gene account for a half of the affected individuals. We describe a family with CdLS carrying a novel pathogenic variant of the SMC1A gene identified by exome sequencing. The proband was a 3-yr-old boy presenting with a developmental delay. He had distinctive facial features without major structural anomalies and tested negative for the NIPBL gene. His younger sister, mother, and maternal grandmother presented with mild mental retardation. By exome sequencing of the proband, a novel SMC1A variant, c.3178G>A, was identified, which was expected to cause an amino acid substitution (p.Glu1060Lys) in the highly conserved coiled-coil domain of the SMC1A protein. Sanger sequencing confirmed that the three female relatives with mental retardation also carry this variant. Our results reveal that SMC1A gene defects are associated with milder phenotypes of CdLS. Furthermore, we showed that exome sequencing could be a useful tool to identify pathogenic variants in patients with CdLS.
Asian Continental Ancestry Group/genetics ; Base Sequence ; Cell Cycle Proteins/*genetics ; Child, Preschool ; Chromosomal Proteins, Non-Histone/*genetics ; DNA ; DNA Mutational Analysis ; De Lange Syndrome/diagnosis/*genetics ; Female ; Heterozygote ; Humans ; Male ; Pedigree ; Phenotype ; Polymorphism, Single Nucleotide ; Proteins/genetics ; Republic of Korea

Fanconi's anemia (FA) is a rare familiar form of aplastic anemia (AA) that is associated with increased chromosomal instability and defective DNA repair, and it characterized by progressive pancytopenia, skeletal abnormalities, hyperpigmentation, and an increased risk of leukemia, hepatocellular carcinoma (HCC) and squamous cell carcinoma (SCC), including head and neck SCC. We reported a 31-year-old man who had AA for 17 years and who developed SCC of oral cavity and then metachronously developed HCC. For treatment of his AA, he was given cyclosporin, steroid and androgen in addition to frequent blood transfusion. At the age of 27, he presented with SCC of the maxilla and the right maxillectomy was performed. Four years later in 2003, hepatic resection of the left medial segment of the liver was performed due to hepatocellular carcinoma. Confirmation of FA was done by cytogenetic analysis. The patient died in 2005 of subdural hemorrhage and pneumonia without involvement of the SCC and HCC.
Adult ; Anemia, Aplastic ; Blood Transfusion ; Carcinoma, Hepatocellular* ; Carcinoma, Squamous Cell* ; Chromosomal Instability ; Cyclosporine ; Cytogenetic Analysis ; DNA Repair ; Fanconi Anemia* ; Head ; Hematoma, Subdural ; Humans ; Hyperpigmentation ; Leukemia ; Liver ; Maxilla ; Mouth* ; Neck ; Pancytopenia ; Pneumonia

BACKGROUND: Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea. METHODS: AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues. RESULTS: AURKA gene amplification was found more frequently in the 20q13.2–13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001). CONCLUSIONS: AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients.
Adenocarcinoma* ; Aurora Kinase A* ; Chromosomal Instability ; Colorectal Neoplasms ; Comparative Genomic Hybridization ; Disease-Free Survival ; Fluorescence ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Korea ; Male ; Mitosis ; Multivariate Analysis ; Phosphotransferases ; Prognosis ; Proportional Hazards Models

Triplication of 1q is a very rare chromosomal abnormality in hematologic malignancies, and it has been related to Fanconi anemia. The clinical significance of this abnormality is unknown. We report here on a 55-year-old female patient who had myelodysplastic syndrome (refractory anemia with excess blasts) with triplication of 1q and trisomy 8 as the clonal cytogenetic abnormalities, as determined by bone marrow cytogenetic analysis. However, there were no clinical manifestations of Fanconi anemia or any chromosomal instability according to the peripheral blood chromosomal breakage testing. The patient developed early gastric carcinoma (poorly differentiated adenocarcinoma with a signet ring cell component) eight months later. She continuously had pancytopenia with dysplastic features, but this showed no evidence of evolving to leukemia or any relapse of the gastric carcinoma over a 2 year follow up.
Adenocarcinoma ; Anemia ; Bone Marrow ; Chromosomal Instability ; Chromosome Aberrations ; Chromosome Breakage ; Cytogenetic Analysis ; Fanconi Anemia ; Female ; Follow-Up Studies ; Hematologic Neoplasms ; Humans ; Leukemia ; Middle Aged ; Myelodysplastic Syndromes* ; Pancytopenia ; Recurrence ; Trisomy

Among several newly identified oncogenes, dek and af4 are attractive targets for researchers interested with leukemia. In this study quantitative Real-Time RT-PCR technique was used to define alterations in expression of dek and af4 genes associated with acute promyelocytic leukaemia (APL) t (15; 17). RNA samples obtained from bone marrow aspirates of fourteen APL patients, cDNA portions were labelled with Syber Green 1 dye and LightCycler analysis have been performed. Expression changes in patients were found not significant in comparison to healthy donors for af4 (P=0.192) and dek (P= 0.0895). We suggest that af4 gene may have a role in leukomogenesis restricted to lymphoblastic lineage; also further studies must carry on with a larger series of patients in order to understand the relationship between the dek gene and APL. Our study was the first attempt for analysing dek and af4 genes in APL t (15; 17) patients by quantitative Real-Time RT-PCR. This rapid and sensitive method could be used to screen these genes in different types of leukaemia.
Adolescent ; Adult ; Child ; Child, Preschool ; Chromosomal Proteins, Non-Histone/*genetics/metabolism ; Chromosomes, Human, Pair 15 ; Chromosomes, Human, Pair 17 ; DNA-Binding Proteins/*genetics/metabolism ; Down-Regulation ; Female ; Gene Expression ; Humans ; Leukemia, Promyelocytic, Acute/*genetics/metabolism ; Male ; Middle Aged ; Nuclear Proteins/*genetics/metabolism ; Oncogene Proteins/*genetics/metabolism ; Polymerase Chain Reaction ; RNA, Messenger/analysis/metabolism ; Translocation, Genetic ; Up-Regulation

OBJECTIVETo investigate mutations of MECP2 gene in classical sporadic Rett syndrome (RTT) patients in China.

METHODSPolymerase chain reaction, single strand conformation polymorphism, cloning and direct sequencing were employed to analyse the three exons of MECP2 gene in 26 RTT patients and their parents, and in 2 sisters of 2 of the RTT patients.

RESULTSNine different mutations in exon 3 were identified in 14 of the 26 patients with RTT, including 3 missense mutations, 3 nonsense mutations, and 3 frame-shift mutations (2 deletion mutations and 1 insert mutation); 2 of these were novel. A missense variant was also identified, which was carried by unaffected father and affected daughter.

CONCLUSIONMutations in MECP2 gene were found over 50% of patients with RTT in China.

Base Sequence ; Child ; Child, Preschool ; Chromosomal Proteins, Non-Histone ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; DNA-Binding Proteins ; genetics ; Female ; Humans ; Infant ; Methyl-CpG-Binding Protein 2 ; Mutagenesis, Insertional ; Mutation ; Mutation, Missense ; Polymorphism, Single-Stranded Conformational ; Repressor Proteins ; Rett Syndrome ; genetics ; Sequence Deletion

OBJECTIVERett syndrome (RTT) is a neurodevelopmental disorder which causes severe mental retardation. This study aimed at elucidating clinical features of 66 Chinese RTT cases diagnosed by The Department of Pediatric Neurology, Peking University First Hospital since 1987, and at analysis of the MeCP2 genotype / phenotype correlation.

METHODSSixty-six RTT cases were followed up every one to two years to get the information of their clinical manifestations and the response to the L-carnitine treatment which was administered to the patients at a dose of 80-100 mg/(kg d). MeCP2 mutation analysis by PCR and sequencing were performed on 39 cases.

RESULTSIn this cohort of cases, the onset of the disease occurred between 3 and 38 months of age, 89% of the cases lost their purposeful hand use at 7 months to six years of age, all the cases had stereotype hand movement which presented at 1 to 5 years of age, 85% of the cases lost language ability at 11 months to eight years of age, 21% of the cases lost the ability of walking at ages of 2 years and 9 months to 15 years. The symptoms/signs such as small head circumference, seizures, breathing irregularities, teeth grinding, scoliosis/ kyphosis were presented in many of the cases. The clinical manifestations were improved in 6 cases after L-carnitine treatment. MeCP2 gene mutation was found in 64% of the cases. Two cases with non-sense mutation C502t (amino acid change R168X) died, two cases with missense mutation C397T (amino acid change R133C) and one case with missense mutation A398T (amino acid change R133H) preserved several words.

CONCLUSIONDeceleration of the head growth, loss of acquired purposeful hand use, stereotype hand movement and language deterioration were the main characteristics of RTT. L-carnitine could improve the clinical manifestation of some cases. There are some correlations between MeCP2 genotype and phenotype.

Adolescent ; Carnitine ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Chromosomal Proteins, Non-Histone ; genetics ; DNA Mutational Analysis ; DNA-Binding Proteins ; genetics ; Female ; Follow-Up Studies ; Genotype ; Hospitals, University ; Humans ; Infant ; Male ; Methyl-CpG-Binding Protein 2 ; Mutation ; Phenotype ; Repressor Proteins ; genetics ; Rett Syndrome ; drug therapy ; genetics ; pathology ; Treatment Outcome