1/6. Molecular cytogenetic analysis of a duplication Xp in a female with an abnormal phenotype and random X inactivation.We describe a female infant with severe abnormal phenotype with a de novo partial duplication of the short arm of the x chromosome. chromosome painting confirmed the origin of this X duplication. Molecular cytogenetic analysis with fluorescence in situ hybridization (FISH) was performed with YAC probes, further delineating the breakpoints. The karyotype was 46, X dup(X)(p11-p21.2).Cytogenetic replication studies showed that the normal and duplicated X chromosomes were randomly inactivated in lymphocytes. In most females with structurally abnormal X chromosomes, the abnormal chromosome is inactivated and they are phenotypically apparently normal relatives of phenotypically abnormal males having dupX. Therefore, in this case, there is functional disomy of Xp11-p21.2 in the cells with an active dup(X), most likely resulting in abnormal clinical findings in the patient.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/6. Hepatocyte nuclear factor-1beta: a new kindred with renal cysts and diabetes and gene expression in normal human development.The hepatocyte nuclear factor-1beta (HNF-1beta) transcription factor controls endoderm development. Human mutations cause early-onset diabetes mellitus and have recently been associated with dysplastic, hypoplastic, and glomerulocystic kidneys. A new kindred with this "renal cysts and diabetes" syndrome is described, and nephrogenic HNF-1beta expression is defined. The proband had congenital cystic kidneys: over the next 12 yr, his renal function was impaired, but he was normoglycemic. His mother developed diabetes during pregnancy: renal ultrasonography at age 24 yr was normal, but she subsequently developed cysts. Both subjects have a heterozygous frameshift mutation in HNF-1beta that results from a 1-bp insertion in exon 5 (Y352fsinsA). When reverse-transcription PCR and in situ hybridization were used, HNF-1beta mRNA was detected in normal human metanephroi, with the highest levels of transcripts localized to fetal medullary and cortical collecting ducts and low levels of expression in nephrogenic cortex mesenchyme, primitive nephron tubules, and immature glomeruli. These results constitute the first demonstration of HNF-1beta expression during human nephrogenesis and emphasize a disease spectrum associated with HNF-1beta mutation.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/6. Microchimerism in a female patient with systemic lupus erythematosus.Systemic lupus erythematosus (SLE) is a serious multisystem disease that has a striking propensity to affect women. The cause of SLE remains elusive. Fetomaternal cell trafficking, or the passage of fetal cells into the maternal circulation, is now a well-established phenomenon. In addition, fetal cells have been implicated in the development of preeclampsia and in the pathogenesis of scleroderma. We undertook this study to determine whether fetomaternal cell trafficking might also be involved in pathogenic processes in SLE. fluorescence in situ hybridization analysis was performed using X and y chromosome-specific probes on affected and unaffected tissue obtained at autopsy from a woman who had previously given birth to 2 males and who had died of complications of SLE. The goal of the analysis was to detect the presence of male cells of putative fetal origin. Male cells were found in every histologically abnormal tissue type that was examined, but were not found in histologically normal tissue. These data suggest that fetal cells may be associated with SLE. It is unclear whether their presence may be related to disease causation, an effect of disease progression, or unrelated to disease pathology. However, this case study is an important step toward understanding the potential relationship between fetomaternal cell trafficking and SLE pathology.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/6. Further case of Cantu syndrome: exclusion of cryptic subtelomeric chromosome aberrations.Cantu syndrome consists of hypertrichosis, osteochondrodysplasia, and cardiomegaly, and has been reported in 18 patients to date. We report an infant with Cantu syndrome. In addition to typical findings, he had relatively mild radiological and cardiological manifestations. Previously undescribed findings included pyloric stenosis and elevated alkaline phosphatase levels. brain scans showed bilateral calcification of the Arteriae thalamostriatae and widening of the outer liquor spaces and lateral ventricles. Because the propositus is the youngest patient reported to date, our findings refine the clinical spectrum of Cantu syndrome in neonates and young infants. The etiology and mode of inheritance of Cantu syndrome are unknown. Most cases are sporadic. Microdeletions have been discussed as a possible cause of Cantu syndrome. Recently, several syndromes with multiple congenital anomalies and mental retardation have been shown to be caused by subtelomeric chromosome aberrations. We excluded the presence of a cryptic subtelomeric chromosome anomaly in our patient by fluorescence in situ hybridization (FISH) screening with locus-specific probes.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/6. Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta.BACKGROUND: Mesenchymal stem cells (MSC) are progenitors of mesenchymal tissues such as bone, cartilage, and adipose. adult human leukocyte antigen (HLA)-matched MSC have been used in cellular therapies of bone disorders such as osteogenesis imperfecta, with promising results. methods: A female fetus with multiple intrauterine fractures, diagnosed as severe osteogenesis imperfecta, underwent transplantation with allogeneic HLA-mismatched male fetal MSC in the 32nd week of gestation. Engraftment analyses of donor cells, immunologic reaction against donor cells, and the well-being of the patient were assessed. RESULTS: At 9 months of age, on slides stained for osteocalcin or osteopontin, a centromeric XY-specific probe revealed 0.3% of XY-positive cells in a bone biopsy specimen. Whole Y genome fluorescent in situ hybridization staining showed a median of 7.4% Y-positive cells (range, 6.8%-16.6%). Bone histology showed regularly arranged and configurated bone trabeculae. Patient lymphocyte proliferation against donor MSC was not observed in co-culture experiments performed in vitro after MSC injection. Complementary bisphosphonate treatment was begun at 4 months. During the first 2 years of life, three fractures were noted. At 2 years of corrected age, psychomotor development was normal and growth followed the same channel, -5 SD. CONCLUSIONS: The authors' findings show that allogeneic fetal MSC can engraft and differentiate into bone in a human fetus even when the recipient is immunocompetent and HLA-incompatible.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/6. Hybridization of chromosome 18 alpha-satellite dna probe to chromosome 22.fluorescence in situ hybridization (FISH) of uncultured chorionic villus diploid cells with a chromosome 18 alpha-satellite dna probe (D18Z1) revealed a third small signal in addition to two large signals. FISH analysis of diploid metaphase cells from cultured chorionic villus cells and from maternal lymphocytes revealed that the third signal resulted from hybridization to the centromere of chromosome 22. This is the first report of a variant involving D18Z1 detected by FISH and of hybridization of alpha-satellite from a sub-metacentric chromosome to the centromere of an acrocentric chromosome. We propose that this inherited variant resulted from insertion of chromosome 18 specific alpha-satellite dna sequences into the centromeric region of chromosome 22.- - - - - - - - - - ranking = 3keywords = hybridization (Clic here for more details about this article) |