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O Bartsch

Publications and source records attributed to O Bartsch.

At least 37 records · Page 2Linked to original sources
PubMed1999

Identification of cyclin A/Cdk2 phosphorylation sites in B-Myb.

B-myb is a highly conserved member of the myb proto-oncogene family that encodes a ubiquitously expressed 110-kDa sequence-specific DNA-binding protein. Transactivation of Myb-inducible promoters by B-Myb is repressed by a regulatory domain located at the C-terminus of the protein. Cyclin A/Cdk2-mediated phosphorylation apparently releases the negative constraint and triggers B-Myb transactivation potential. Two-dimensional tryptic phosphopeptide analysis indicated that the majority of the sites phosphorylated in vivo are targeted in vitro by cyclin A/Cdk2. Six sites in B-Myb fulfil the requirements for recognition by Cdk2. Using point mutation of the phosphorylation sites to nonphosphorylatable amino acids, we show that five of these sites are targets for Cdk2 in vivo. Mutation of one of these residues (T524) to alanine diminished the ability of B-Myb to promote transcription of a reporter gene, suggesting that phosphorylation of B-Myb at this site is important for the regulation of its activity by cyclin A/Cdk2.

Amino Acid Substitution↗
PubMed1999

The novel contiguous gene syndrome of myotubular myopathy (MTM1), male hypogenitalism and deletion in Xq28:report of the first familial case.

Hu et al. (1996) and Laporte et al. (1997) recently proposed a novel contiguous gene syndrome of myotubular myopathy, abnormal male genital development and deletion in Xq28. We studied a family where two male infants, both deceased, had myotubular myopathy and intersexual genitalia. Using FISH we detected in the mother a hemizygous deletion including the myotubularin gene MTM1 and F18 (a gene of yet unknown function). DNA studies with STR-markers (short tandem repeats) within and flanking the deleted segment confirmed the deletion in the family and were used for prenatal diagnosis. Our findings confirm the existence of this novel contiguous gene syndrome and support that the deletion of the F18 gene, or a neighboring gene, may cause ambiguous genitalia or severe hypospadias in males. The mother had low muscle power and marked menstrual irregularities which may indicate that she is a manifesting carrier and that the deletion may include a gene (F18 or other) for gonadal function in females.

Adult↗
PubMed1998

Familial Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS) occurs sporadically; however, at least four familial cases of WBS have been described previously. We describe a mother and her son with typical WBS. The diagnosis of WBS in the son was confirmed by molecular cytogenetic analysis fluorescence in situ hybridization. He had a deletion of 7q11.23 at the ELN locus. The mother was diagnosed after the identification of WBS in her affected son. She is deceased and was thus not studied by FISH. However, her combined symptoms make it very clear that she had WBS. Two traits uncommon in WBS were observed, unilateral renal hypoplasia in the mother and a hemivertebra at L5 in the son.

Adult↗
PubMed1998

Deletion mapping by FISH with BACs in patients with partial monosomy 22q13.

Patients with deletions in 22q13 are known to have phenotypic features that include normal or accelerated growth, large hands and feet, hypotonia, delayed psychomotor development and mild facial dysmorphism. To date, very few cases have been investigated by detailed molecular genetic analysis. We have analyzed three new patients with terminal deletions in 22q. We compared the cytogenetic observations with molecular data assessed by fluorescence in situ hybridization and an array of characterized bacterial artificial chromosome recombinants. The shortest region of deletion overlap is localized in 22q13.2-qter distal to the marker D22S94, but the telomeric repeat in the deleted chromosome appears to remain intact. When parental alleles were investigated in two of the three patients, the aberrant homolog was found to be of paternal origin in both cases. Although the deleted region still spans >20 cM, molecular analysis of additional patients and screening for new genes might help in elucidating candidate genes connected with the dysmorphisms defined by deletions of 22q13.

Child, Preschool↗
PubMed1997

A small deletion of 16q23.1-->16q24.2 [del(16)(q23.1q24.2).ish del(16)(q23.1q24.2)(D16S395+, D16S348-, P5432+)] in a boy with iris coloboma and minor anomalies.

We report on a 5-year-old boy with bilateral coloboma of iris, short stature, moderate developmental delay, and a few minor craniofacial anomalies. High-resolution GTG banding showed a small distal deletion of one chromosome 16 [del(16)(q23.1q24.2)]. Molecular refinement of the deletion breakpoints yielded that the proximal breakpoint at 16q23.1 is located between loci D16S395 (present) and D16S348 (absent). Comparison with previously published cases of deletion 16q demonstrated that the clinical phenotype is not a recognizable 16q- syndrome and different from the two cases of deletions of 16(q22.1 to q24.1) described by Callen et al. [1993]. Evidently, deletion 16(q23.1q24.2) has a milder phenotypic effect than other interstitial and distal 16q deletions.

Child, Preschool↗
PubMed1997

Phosphorylation and activation of B-Myb by cyclin A-Cdk2.

BACKGROUND: Cyclins and their catalytic partners, the cyclin-dependent kinases (Cdks), function as key regulators of the eukaryotic cell cycle. Specific cyclin-Cdk complexes are active at successive stages during the cell cycle and control cell-cycle progression by phosphorylating specific target proteins, most of which have not yet been identified. B-Myb, a conserved member of the Myb oncoprotein family, is a sequence-specific DNA-binding protein expressed in virtually all proliferating mammalian cells. Increasing evidence suggests that B-Myb plays an important role during the late G1 and early S phases of the cell cycle. In this study, we have examined the regulation of B-Myb activity by cyclin-Cdks. RESULTS: We found that the transcriptional transactivation potential of B-Myb was repressed by a regulatory domain located at the carboxyl terminus of the protein. Coexpression of B-Myb and cyclin A relieved this repression by phosphorylation of B-Myb in its carboxy-terminal region. Tryptic phosphopeptide mapping revealed that endogenous B-Myb was phosphorylated in cells undergoing S phase. CONCLUSIONS: This work provides evidence for a link between the Myb oncoprotein family and the cell-cycle machinery. We have shown that the carboxyl terminus of B-Myb acts as a cell-cycle sensor that regulates the transactivation function of B-Myb. Moreover, our studies have identified B-Myb as a target of cyclin A-Cdk2 and have indicated that B-Myb activity is regulated by phosphorylation mediated by cyclin A-Cdk2.

3T3 Cells↗
PubMed1997

A large family with subtelomeric translocation t(18;21)(q23;q22.1) and molecular breakpoint in the Down syndrome critical region.

We describe a 17-month-old infant with clinical features of Down syndrome and a normal karyotype by standard chromosomal analysis, her two uncles aged 28 and 30 years, respectively, with reduced intelligence and unusual appearance but not apparent Down syndrome, and a severely retarded 6-year-old girl with dysmorphy and epilepsy from the same family. Cytogenetic studies of patients and normal intervening relatives had been carried out at different institutions with normal results. Fluorescence in situ hybridization using whole chromosome painting and unique-copy probes (cosmids) and high-resolution banding revealed a familial subtelomeric translocation of chromosomes 18 and 21, resulting in partial trisomy 21 in the infant and her two uncles, and partial monosomy 21 in the 6-year-old girl. Cytogenetic breakpoints were located in bands 18q23 and 21q22.1, respectively. The molecular breakpoint on chromosome 21 was located between D21S211 (proximal) and D21S1283 (distal) and thus maps within the Down syndrome critical region.

Adult↗
PubMed1996

Evidence for a critical region for penoscrotal inversion, hypospadias, and imperforate anus within chromosomal region 13q32.2q34.

Two unrelated patients with small distal deletions of the long arm of chromosome 13 are described, with shawl scrotum and penoscrotal transposition, penoscrotal hypospadias, a reduced perineum, and anal atresia. The patients have small deletions of 13(q32.2qter) and 13(q32q34), respectively. This report and the literature present evidence for one or possibly more gene(s) within region 13q32.2q34 which regulate the development of the ano-genital structures. The clinical spectrum includes bifid or shawl scrotum, hypospadias, biseptate uterus, malplaced and imperforate anus, and common cloaca.

Anus, Imperforate↗
PubMed1996

Derivative (6)t(1;6)(q22;p21) revealed in bone marrow cells by FISH 9 months before diagnosis of acute T-lymphoblastic leukemia.

A chromosomal clone with unbalanced translocation resulting in partial trisomy of segment 1q22-qter and partial monosomy of segment 6p21-pter was revealed by fluorescence in situ hybridization (FISH) using a panel of different whole chromosome painting probes. The pathologic clone appeared after sequential chemotherapy treatment for AML-M5 when the patient was in complete remission before development of T-ALL. However, this clone was present during the whole period of treatment for T-ALL. The clone remained the only chromosomal aberration found. Breakpoints were detected more easily and more precisely with the use of the FISH technique than with G-banding only.

Bone Marrow↗
PubMed1996

Delineation of a contiguous gene syndrome with multiple exostoses, enlarged parietal foramina, craniofacial dysostosis, and mental retardation, caused by deletions in the short arm of chromosome 11.

A contiguous gene syndrome due to deletions of the proximal short arm of chromosome 11 is described in eight patients belonging to four families. The main clinical features are multiple exostoses, enlarged parietal foramina, craniofacial dysostosis, and mental retardation. The patients have cytogenetic and/or molecular deletions of chromosome 11p11-p13. These deletions are located between the centromere and D11S914 in a region of approximately 20cM. The present study confirms the presence of a multiple exostoses gene on chromosome 11p. Furthermore, it suggests that the gene for isolated foramina parietalie permagna and genes associated with craniofacial dysostosis and mental retardation reside in the same chromosomal region.

Abnormalities, Multiple↗
PubMed1995

DNA, FISH and complementation studies in ICF syndrome: DNA hypomethylation of repetitive and single copy loci and evidence for a trans acting factor.

ICF syndrome (ICFS) is a rare immunodeficiency disorder characterized by instability of the pericentromeric heterochromatin predominantly of chromosomes 1 and 16. DNA methylation studies in two unrelated ICFS patients provide further evidence for a marked hypomethylation of satellite 2 DNA. The ICFS-specific disturbances of chromatin structure take place within the satellite 2 DNA regions, as demonstrated by fluorescence in situ hybridization analysis. Moreover, methylation studies of genomic imprinted loci D15S63, D15S9, and H19 have revealed hypomethylation to different degrees in both patients; this provides evidence for hypomethylation at autosomal single copy loci in ICFS. Cell fusion experiments have revealed a distinct reduction of chromosomal abnormalities in ICFS cells after fusion with normal cells, suggesting that the abnormalities are caused by the loss of function of an as yet unknown trans acting factor. Although it is now clear that wide-spread DNA hypomethylation is a characteristic feature of ICFS, neither the cause and mechanism of hypomethylation nor their relationship to the clinical symptoms is known. We speculate that a phenotypic effect might result from tissue-dependent abnormal gene expression and/or from a possible structural disturbance of DNA domains, which, with respect to the immunodeficiency, partially prevents the normal somatic recombinations in immunologically active cells.

Cell Line, Transformed↗
PubMed1995

Fryns syndrome: two further cases without lateral diaphragmatic defects.

We report on two unrelated infants with Fryns syndrome but without lateral diaphragmatic defects. In case 1, a female stillborn, pertinent findings included a coarse facies, cleft palate, short neck with a broad pterygium, heart defect, lung hypoplasia, omphalocele, urogenital malformations, anal atresia, and distal digital hypoplasia. Case 2 showed a coarse facies with cleft lip and palate, para-oesophageal hernia with herniation of the stomach into the thoracic cavity, malrotation of the intestine, hydronephrosis, and anal atresia. At age 14 months she was developmentally severely retarded. These observations represent the 11th and 12th reports of probable Fryns syndrome without lateral diaphragmatic defect.

Abdomen↗
PubMed1994

"Compensatory" uniparental disomy of chromosome 21 in two cases.

Two cases of growth failure, microcephaly, facial dysmorphism, muscular hypertonia, and severe psychomotor retardation are described. At birth, both cases had cytogenetic mosaicism in lymphocytes and skin fibroblasts, in case 1 ring chromosome 21 and monosomy 21 and in case 2, deletion of chromosome 21 and monosomy 21. At a later age the lymphocyte karyotype changed almost completely to 46,XX, but the fibroblast karyotype remained as before. DNA polymorphism analysis described elsewhere indicated that the 46,XX lymphocytes contained two identical chromosomes 21 (isodisomy), in case 1 inherited from the father and in case 2 from the mother. The isodisomy was the result of duplication of a chromosome in mitosis after the loss of the homologous abnormal chromosome ("compensatory isodisomy"). We report here that this cytogenetic mechanism can result in false normal cytogenetic findings. The phenotypes were attributed to the cells with monosomy 21 in case 1 and to the deletion and monosomy of chromosome 21 in case 2.

Adolescent↗
PubMed1994

Mulvihill-Smith syndrome: case report and review.

We report a 20 year old man with short stature, microcephaly, unusual facies, numerous pigmented naevi, hypodontia, immunodeficiency, and a high pitched voice. Tympner et al had assumed that the patient had a new syndrome of "progressive combined immunodeficiency and ectomesodermal dysplasia". We show here that the condition is identical to the Mulvihill-Smith syndrome (McKusick 176690), a progeroid disorder described in four or possibly five sporadic cases to date. We describe his clinical progress up to the age of 20 years. Our patient suffered from severe viral infections, allergic rhinitis and conjunctivitis, delayed puberty, visual loss, modest achievement in high school, and reactive depression. The immunological, facioskeletal, and dental abnormalities are presented in detail.

Abnormalities, Multiple↗
PubMed1993

Cytogenetic, FISH and DNA studies in 11 individuals from a family with two siblings with dup(21q) Down syndrome.

A Spanish family has previously been described with two siblings with dup(21q) Down syndrome. The father has a normal karyotype. The mother has a microchromosome. Cytogenetic, fluorescence in situ hybridization and DNA studies have now been carried out on the family. Findings include that the mother has three different chromosome anomalies, viz. (1) a chromosome 22 with an unusual pericentromeric region that contains alphoid DNA from chromosomes 21/13 and chromosome 22, (2) an isochromosome 21p in the frequent cell line and (3) an isochromosome 21q in a rare second cell line. A possible explanation is that the mother developed from a zygote with trisomy 21 and that mitotic error in early development resulted in the formation of two cell lines with karyotypes of 47,XX,+i(21p) and 47,XX,+i(21q), respectively. The unusual chromosome 22 represents a hitherto undescribed chromosome anomaly and one possible explanation is a translocation of the short arms between chromosomes 21/13 and 22 in the ancestry of the family. The relationship between the unusual chromosome 22 and the isochromosome formation in the mother is not known. However, all three chromosome anomalies involve the alphoid DNA of chromosome 21/13, indicating that this is not a chance finding.

Centromere↗
PubMed1993

Partial trisomy of 3q detected by chromosome painting in a case of juvenile chronic myelomonocytic leukemia.

Juvenile chronic myelomonocytic leukemia (JCMMoL) is a rare disease with no specific type of chromosome aberration yet delineated. We report a 2-year-old boy who had in his leukemic bone marrow (BM) and peripheral blood (PB) cells the 46,XY,der(15)t(3;15)(q13.1;q26) karyotype. Phytohemagglutinin (PHA)-stimulated lymphocytes of peripheral blood had a normal 46,XY karyotype. The origin of the duplicated part of 3q was proved by fluorescence in situ hybridization (FISH) with the pHSR(sat III 15p) DNA probe and a chromosome 3-specific DNA library (i.e., chromosome painting). The chromosome finding in our case provides further proof of the close relationship between the rearrangement in region 3q13-->3q26 and the pathogenesis of acute myeloid leukemia (AML). Our patient has transformed into erythroleukemia [M6 according to the French-American-British (FAB) classification] during the course of the disease.

Cell Division↗
PubMed1992

Uniparental isodisomy due to duplication of chromosome 21 occurring in somatic cells monosomic for chromosome 21.

Uniparental disomy has been recently recognized as an important phenomenon in non-Mendelian inheritance of human genetic disorders. Several mechanisms for uniparental disomy, i.e., the presence of two homologous chromosomes derived from one parent, have been proposed. We studied two independent cases of abnormalities of chromosome 21 in which there were abnormal karyotypes at birth but blood cells with normal karyotype predominated later in life, and the cells with abnormalities disappeared. Uniparental isodisomy was observed in the normal cells in these individuals. The uniparental disomy in these families was the result of duplication of a chromosome in mitosis after the loss of the homologous abnormal chromosome. The duplication can be seen as mechanism for cell survival and is called here "compensatory" isodisomy, which provided a selective advantage for the cell population with the normal number of chromosomes 21.

Abnormalities, Multiple↗