Christa Fonatsch

Preferential Maternal Derivation in Inv Dup(15) Analysis of Eight New Cases

SummaryEight patients are reported with a de nov extra inverted duplicated chromosome 15. The abnormal chromosome was considered to be the same in all cases, but its precise delineation remained uncertain and was defined as either 15qter→15q12::15q12→15pter or 15pter→15q11::15q13→15pter. Analysis with various techniques of the satellite regions of the bisatellited chromosomes demonstrated maternal derivation in six and paternal derivation in one of the seven families. A nonsister chromatid exchange between the two homologous chromosomes 15 is considered a likely origin of the inv dup(15) in the cases with maternal derivation; in the only case of paternal derivation, however, the abnormal chromosome originated from one single chromosome 15. The clinical findings confirm that patients with inv dup(15) have mental and developmental retardation and are frequently affected by seizures, while severe physical malformations are absent.

Establishment of a malignant, epstein-barr-virus (EBV)-negative cell-line from the pleura effusion of a patient with Hodgkin's disease

The pleura effusion was obtained from a 37-year-old woman with histologically proven Hodgkins disease, nodular sclerosing type, stage IVB, primarily diagnosed in 1972. In the 4 weeks before the last admission to our institution, the patient developed a severe eosinophilia (91 ~), the total WBC amounted to 26000/ram 3. The nodal and extranodal tumor progression did not respond to a polychemotherapy (MOPP) and the patient died due to a septical complication. The post mortem showed beside a disseminated lymphnode involvement extranodal invasion of the whole left-side chest-wall including the parietal pleura.

A Simple Method to Demonstrate the Fragile X Chromosome in Fibroblasts

Since the detection of a fragile site on the long arm of the X chromosome in lymphocytes of patients with X-linked mental retardation, attempts have been made to demonstrate the fragile X chromosome [fra(X)] in fibroblasts and amniotic fluid cells for prenatal diagnosis (Jacky and Dill 1980; Tommerup et al. 1981). Prenatal diagnosis requires an easily and rapidly practicable technique with clear results. Referring to our previous observations (Fonatsch 1981), we studied the effect of folic acid antagonists on fibroblast cultures. Skin biopsy from an affected male was obtained by Professor Schwinger (Liabeck), who demonstrated the fra(X) in the patients lymphocytes. Fibroblast primary cultures were set up in T-15 glass flasks (Bellco) in Hams F 10 or Dulbeccos medium supplemented with 20% fetal calf serum (FCS). Subcultures were made after trypsinization and maintained in T-25 plastic flasks (Falcon) in medium containing 20% or 10% FCS. Cells in the second to sixth passages were used for the demonstration of fra(X). Immediately after subculturing or 24h later, methotrexate (MTX, 10lag/ml culture medium) or aminopterine (AP, 16 lag/ ml culture medium) was added. The incubation with MTX or AP lasted 24 h. After treatment with colcemid (1 lag/ml culture medium) for 5h, the cells were removed by trypsinization, centrifuged, treated with hypotonic solution (0.075M KC1) for 20min, fixed by a mixture of methanol and acetic acid (3:1), dropped on ice-cold slides, air dried, and treated by conventional Giemsa staining and G-banding techniques. A high number of analyzable metaphases can be produced

Replication pattern in XXY cells with fra(X)

SummaryClinical and cytogenetic aspects, including replication studies, of a Klinefelters patient with fra(X) are reported. In the majority of metaphases the fragile site was observed at the early replicating X chromosome.

Partial trisomy 1q due to tandem duplication.

Sirs, Rehder & Friedrich (1979) recently described partial trisomy l q syndrome and summarized the characteristic symptoms. These observations may be supplemented by the case of a boy (now aged 9 months) in whom similar clinical features enabled us to identify a de novo elongation of the long arm of chromosome 1 as tandem duplication. The boy is the second child of healthy, 21-year-old parents. He was born by breech delivery after 37 weeks of gestation. His birth weight was 2310 g, and his length 46 cm. Growth and development were delayed. Physical examination at the age of 6 weeks revealed a hydrocephalic configuration of the skull with large fontanelles and a wide open sagittal suture, a prominent forehead and a small triangular face with a small, pointed chin. There was mid-facial hypoplasia, deeply set eyes, upward slanting of the palpebral fissures and biepharophimosis. The bridge of the nose was depressed, the nose was beaked a t the tip with a long nasal septum and anteverted nostrils. The

Non‐fluorescent Y chromosome in a male infant with Turner's symptoms and XO/XY mosaicism

A 45,X/46,XY mosaicism was found in a male infant with stigmata of Turners syndrome but normal male external genitalia. In contrast to the Y chromosome of his father, the Y chromosome of the patient does not display either the characteristic brilliant fluorescence or the typical dark heterochromatin staining of the distal long arm. Furthermore, DNA replication in the abnormal Y chromosome was shown to be premature. Mechanisms leading to the observed abnormalities are discussed.

Heterochromatin and nucleolus organizer regions in cells of patients with malignant and premalignant lymphatic diseases

SummaryPeripheral blood lymphocytes (short-term cultures) and permanent lymphoid cell lines (long-term cultures) of patients with Hodgkin disease (5), lymphoma (1),plasma cell leukemia (1), angioimmunoblastic lymphadenopathy (1), and infectious mononucleosis (3) were investigated for C-band variants and nucleolus organizer region (NOR)-activities by C-banding and silver-staining, and compared to those of healthy adults (5) and newborn children (3). Heterochromatin polymorphisms were found in malignant diseases (33%) as well as in controls (29%). In the lymphoma patients, heterochromatin of class 3 (Patil and Lubs 1977) was seen more frequently than in the controls (83%:57%). No marker C-band variants could be detected in any of the lymphatic diseases. There was no difference in the heterochromatin polymorphism between short-term cultures (predominantly T-cells) and long-term cultures (B-cells), and there was little but inconsistant difference in the NOR-activities.Silver-staining showed differences between healthy adults (8.8 AgNORs; SD: 0.5) and newborn children (6.9; SD: 0.4). In the lymphoma patients we found 8.3 (SD: 0.7) AgNORs. Thus, using silver staining there was no detectable increase in the number of active NORs in cells of patients with malignant diseases as an expression of increased nucleolus activation in malignancies. The remarkably low NOR-activity in infectious mononucleosis (6.7; SD: 1.0) may reflect an influence of acute virus infection (Epstein-Barr virus) on NOR-activity.

Partial trisomy 4q and partial monosomy 18q as a consequence of a paternal balanced translocation t(4q−;18q+)

SummaryIn a 16-month-old girl with stigmata of the 18q- syndrome, the analysis of Giemsa banding patterns displayed a chromosome 18 with an enlarged terminal band region of the long arm. The propositas father and brother also revealed an elongated chromosome 18 and, in addition, a shortened long arm of chromosome 4. These two individuals are carriers of a balanced translocation with the karyotype 46,XY,t(4q-;18q+). The proposita received the 18q+ chromosome from the father. She was partially monosomic for a terminal segment of 18q and partially trisomic for a terminal segment of 4q.

The physical map of chromosome arm 19q: some new assignments, confirmations and re-assessments

SummaryWe have constructed and analysed somatic cell hybrids from cell lines containing balanced reciprocal translocations involving chromosome 19 and providing two new breakpoints on 19q. These and other hybrids have been tested with a series of markers from 19q to enhance the existing map. Several new cloned DNA sequences that map to 19q13.3–19qter are reported; the locus D19Z1 has been analysed by CHEF gel electrophoresis.

Sister chromatid exchange in cell lines from malignant lymphomas (lymphoma lines)

SummaryThe frequency of sister chromatid exchanges (SCEs) was studied in cells from three freshly established lymphoma lines, derived from two patients with Hodgkins disease and one patient with non-Hodgkin lymphoma. These values were compared to SCE rates found in cells from two long-established lymphoma lines (Raji and BJAB) and to those recorded in control cell lines of normal human donors. The highest SCE levels were demonstrated in the freshly established lymphoma lines, the lowest SCE values separated the lymphoblastoid cell lines from healthy controls, and the older lymphoma lines Raji and BJAB presented rates in between. The influences of BUDR concentration and of the duration of BUDR treatment on the frequency of SCEs were tested. Furthermore, the dependence of the SCE rate on the time interval between establishment of the cell line and its SCE investigation was considered. The connection between elevated SCE rates and the neoplastic nature of lymphoma lines is discussed.