1/10. A microdeletion syndrome due to a 3-Mb deletion on 19q13.2--diamond-Blackfan anemia associated with macrocephaly, hypotonia, and psychomotor retardation.We report on a boy with congenital pure red blood cell aplasia [diamond Blackfan anemia (DBA)] and severe congenital hypotonia, macrocephaly, hypertelorism, a broad and tall forehead, medial epicanthus, and facial hypotonia with mouth-breathing and drooling, an affable and out-going personality, and a general psychomotor retardation. These features show similarity to the phenotype of the X-linked FG syndrome. DBA was diagnosed at the age of 4 months, and the boy underwent treatment with transfusion and with prednisolone. He had a normal 46, XY karyotype, but fluorescence in situ hybridization (FISH) analysis to metaphase chromosomes revealed a 3-Mb deletion on 19q13.2. This chromosomal region has previously been linked to the DBA phenotype and one 19q13 microdeletion has been identified in a patient with DBA. This deletion coincides with the deletion reported here. We suggest that the complex phenotype of our patient, including both DBA and the associated features, represent a microdeletion syndrome.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
2/10. MLL-CBP fusion transcript in a therapy-related acute myeloid leukemia with the t(11;16)(q23;p13) which developed in an acute lymphoblastic leukemia patient with fanconi anemia.We describe a boy with fanconi anemia (FA) who developed acute lymphoblastic leukemia (ALL) (FAB-LI) followed by acute myeloid leukemia (AML) (FAB-M5) at relapse. The patient was diagnosed with early pre-B-cell ALL without preceding aplastic anemia and was treated with ALL-oriented chemotherapy which included doxorubicin (a total dose of 140 mg/m(2) administered), which is a topoisomerase II inhibitor. Complete remission was obtained, but after 38 weeks AML developed. The karyotype of ALL cells at diagnosis showed 46,XY, and that of AML cells at relapse was 46,XY, t(11;16)(q23;p13). An MLL gene rearrangement and MLL-CBP chimeric mRNA were found in AML, but not in ALL. A diagnosis of FA was confirmed by an increased number of chromosomal breaks and rearrangements in peripheral blood lymphocytes cultured with mitogen in the presence of mitomycin C. We conclude that this FA patient developed ALL followed by a therapy-related t(11;16)-AML resulting in an MLL-CBP fusion. Further examination of such patients would shed light on leukemogenesis in FA patients. genes chromosomes Cancer 27:264-269, 2000.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
3/10. Follow-up by cytogenetic and fluorescence in situ hybridization analysis of allogeneic bone marrow transplantation in two children with Fanconi's anaemia in transformation.Results of bone marrow transplantation (BMT) in patients with Fanconi's anaemia (FA) in transformation are very poor and only a few cases with favourable outcome have been reported. We present the follow-up of two FA-myelodysplastic syndrome (MDS) patients with monosomy 7 and complex karyotype implicating chromosome 1. Both relapsed with acute myeloid leukaemia (AML) following an allogeneic BMT from an HLA-identical brother. The patients showed clonal cytogenetic evolution coinciding with the leukaemic transformation. In one patient, fluorescence in situ hybridization using X and y chromosome probes detected an increase of host cells before clinical relapse. Both patients received a successful second allogeneic BMT from the same donor using a more intensive treatment regimen and remain in clinical and cytogenetic remission more than 3 years later.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
4/10. Two different karyotypes with 1q abnormalities in a patient with fanconi anemia.We report a case of fanconi anemia in which cytogenetic analysis of bone marrow (BM) samples revealed two distinct karyotypes: 46,XY,dup(1)(q21q42), in the first sample and 46,XY,del(1)(q32) in the second, aspirated 7 months later after acute myeloid leukemia (AML) developed. We discuss the cytogenetic clonal fluctuation common in fanconi anemia, with the Fanconi's anemia (FA) reports available in the literature. Interestingly, we have identified that del(1)(q32) has not been reported before in FA.- - - - - - - - - - ranking = 5keywords = karyotype (Clic here for more details about this article) |
5/10. Pentasomy 21 in leukemia complicating diamond-Blackfan anemia.We present the cytogenetic pattern of a leukemic infant with diamond-Blackfan anemia (DBA). The karyotype was characterized by clonal evolution involving consecutive gains of chromosome 21 up to pentasomy. No chromosomal changes were present in normal lymphocytes. Such a karyotype evolution has been described in some cases of acute leukemia associated with down syndrome, but rarely in non-Down cases.- - - - - - - - - - ranking = 2keywords = karyotype (Clic here for more details about this article) |
6/10. Clonal monosomy 7 in a megakaryoblastic leukemia developed on the basis of fanconi anemia.A 13-year-old girl with a history of fanconi anemia developed acute myeloid leukemia of the M7 subtype with a 45,XX,-7 karyotype, which is rare in M7 subtype. Treatment protocols were set up, but she died of sepsis and osteomyelitis during induction.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
7/10. Transformation of Fanconi's anemia to acute nonlymphocytic leukemia associated with emergence of monosomy 7.Two sisters in whom a diagnosis of Fanconi's anemia was made at ages 12 and 18 subsequently developed acute nonlymphocytic leukemia (ANLL). A third sibling had previously died at age 11 of apparent sepsis. Both sisters had cytogenetic studies that showed increased chromosomal breakage and a 46,XX karyotype, but subsequently developed ANLL after, or coincident with, the emergence of monosomy 7. These observations suggest that, in addition to myelodysplastic syndromes and defective neutrophil chemotaxis, monosomy 7 may be associated with the emergence of leukemia in this disorder.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
8/10. Early prenatal diagnosis of Fanconi anaemia in a twin pregnancy, using dna analysis.We present a case of prenatal diagnosis of Fanconi anaemia (FA) in a pair of twins at 14 weeks of gestation. The parents had previously had two children: a healthy boy and a boy with FA belonging to complementation group C (FAC). The FA patient is a compound heterozygote, carrying a 322delG and a IVS4 4A-->T mutation in the FAC gene. Prenatal dna analysis showed that both fetuses were heterozygous for different mutations in the FAC gene. Both fetuses had normal male karyotypes. At 36 weeks the twins were born. They did not show congenital anomalies.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
9/10. in vitro culture studies of childhood myelodysplastic syndrome: establishment of the cell line MUTZ-1.Myelodysplastic syndrome (MDS) in childhood is considered to be very rare and detailed pathobiological data are scarce. More biological information regarding MDS in children is clearly needed and in vitro culture studies provide one possibility for gaining further pathophysiological insights into this malignancy. Here, we incubated bone marrow samples from 30 children with MDS in liquid suspension culture in order to grow the transformed cells in vitro. In most cultures, the hematopoietic cells died quickly and only fibroblastic (stromal) background layers proliferated temporarily; several normal Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines (B-LCL) were established. Only in one instance, albeit from the peripheral blood and not from the bone marrow, could we establish a cell line, termed MUTZ-1, from the malignant cells of a 5-year-old girl with MDS (FAB subtype refractory anemia with excess of blasts). The MDS arose from a pre-existing fanconi anemia and progressed quickly to an acute myeloid leukemia (FAB M2). Despite positivity for EBV, MUTZ-1 is not an EBV B-LCL and further characterization of MUTZ-1 confirmed the derivation from the transformed clonal cells. immunophenotyping showed a pre B-cell surface marker profile (CD10 CD19 cytoplasmic IgM ); receptor gene rearrangement analyses underlined the clonal B-cell nature of MUTZ-1 cells. MUTZ-1 cells exhibit a highly rearranged, unstable karyotype with a high frequency of spontaneous chromatid breaks and exchanges; del(5q) and additional rearrangements involving chromosome 5 [der(15)t(5;15)] were detected. The present data and results from a few other MDS-derived cell lines suggest that the transforming event in MDS seems to occur in an immature pluripotent progenitor cell. The new MDS-derived continuous cell line MUTZ-1 provides a useful in vitro model system for studies on the pathogenetic events leading to MDS.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
10/10. diamond-Blackfan anaemia in a girl with a de novo balanced reciprocal X;19 translocation.A 7 year old girl is described with congenital hypoplastic anaemia (diamond-Blackfan anaemia, DBA) and an apparently balanced reciprocal translocation, 46,XX,t(X;19)(p21;q13). The girl has associated features including short stature, unilateral kidney hypoplasia, and a branchial cyst. Fluorescent in situ hybridisation (FISH) studies with 19q specific cosmids showed that the chromosome 19 breakpoint is located between the RYR1 and the XRCC11 loci spanning a physical region of 5 Mb. There is no family history of DBA and the parents and two healthy sibs have normal karyotypes. This is the first report of a balanced translocation associated with DBA and we suggest that the distinct phenotype has resulted from a de novo disruption of a functional gene. DBA can be inherited as an autosomal trait and our observation may indicate a candidate gene for the disorder in the 19q13 region.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
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