The ataxia-telangiectasia-variant genes 1 and 2 are distinct from the ataxia-telangiectasia gene on chromosome 11q23.1.
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Ataxia Telangiectasia↗
Biomedical subjects
R D Wegner
Publications and source records attributed to R D Wegner.
Fallout from Chernobyl. Authors stand by study that Chernobyl increased trisomy 21 in Berlin.
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Berlin↗
Significant increase in trisomy 21 in Berlin nine months after the Chernobyl reactor accident: temporal correlation or causal relation?
OBJECTIVE: To assess whether the increased prevalence of trisomy 21 in West Berlin in January 1987 might have been causally related to exposure to ionising radiation as a result of the Chernobyl reactor accident or was merely a chance event. DESIGN: Analysis of monthly prevalence of trisomy 21 in West Berlin from January 1980 to December 1989. SETTING: Confines of West Berlin. RESULTS: Owing to the former "island" situation of West Berlin and its well organised health services, ascertainment of trisomy 21 was thought to be almost complete. A cluster of 12 cases occurred in January 1987 as compared with two or three expected. After exclusion of factors that might have explained the increase, including maternal age distribution, only exposure to radiation as a result of the Chernobyl reactor accident remained. In six of seven cases that could be studied cytogenetically the extra chromosome was of maternal origin, confirming that nondisjunction had occurred at about the time of conception. CONCLUSION: On the basis of two assumptions--(a) that maternal meiosis is an error prone process susceptible to exogenous factors at the time of conception; (b) that owing to the high prevalence of iodine deficiency in Berlin a large amount of iodine-131 would have been accumulated over a short period--it is concluded that the increased prevalence of trisomy 21 in West Berlin in January 1987 was causally related to a short period of exposure to ionising radiation as a result of the Chernobyl reactor accident.
Accidents↗
Low-grade non-Hodgkin's lymphoma after high-grade non-Hodgkin's lymphoma in a child with ataxia telangiectasia.
BACKGROUND: Non-Hodgkin lymphomas (NHL) account for approximately 50% of neoplasms in patients with ataxia telangiectasia (AT). Prognosis is poor. Published data regarding the treatment of NHL in patients with AT suggested that these children respond poorly to therapy. The authors report on an infant with AT with mediastinal high-grade T-NHL who remained in continuous complete remission after chemotherapy. Diagnosis of AT was established after tumor diagnosis. METHODS AND RESULTS: The 7-month-old boy was treated according to the acute lymphoblastic leukemia-Berlin, Frankfurt, Münster 86 protocol. The therapeutic response was prompt, but therapy had to be stopped because of severe side effects. Surprisingly, the boy remained in a stable complete remission for 3 1/2 years. Then tumors in both kidneys occurred and the child died a few months later. Postmortem examination demonstrated large tumors in both kidneys caused by a low-grade malignant lymphoma of B-cell lineage. CONCLUSION: Congenital immune deficiency should be ruled out at diagnosis of rare malignancies in respect to age. NHL in patients with AT can be cured, but poor tolerance to chemotherapy has to be considered. Patients whose disease has been cured may be at high risk for development of a second independent malignancy.
Ataxia Telangiectasia↗
Ulerythema ophryogenes and keratosis pilaris in a child with monosomy 18p.
We report a 13-year-old boy with deletion of the short arm of chromosome 18 and follicular, partially inflammatory, keratotic papules of the eyebrows, foreskin, and cheeks (ulerythema ophryogenes) as well as the shoulders, upper back, upper arms, and thighs (keratosis pilaris), initially diagnosed as atopic dermatitis. Over 100 patients with this genetic defect have been reported, and the 18p- syndrome is considered one of the most frequently occurring deletion syndromes. However, ulerythema ophryogenes and keratosis pilaris have not been described in any of these patients, although the association of the latter with other genetic abnormalities is well known. Keratosis pilaris is a relatively common genodermatosis of ectodermal origin, frequently occurring with ichthyosis or atopy; concomitance with ulerythema ophryogenes has also been reported. The association of chromosome 18p deletion defect and ulerythema ophryogenes may be helpful in future attempts to localize the gene defect responsible for follicular genokeratoses.
Child↗
Genetic haplotyping of ataxia-telangiectasia families localizes the major gene to an approximately 850 kb region on chromosome 11q23.1.
The genotyping data given localize the major A-T gene to an approximately 850 kb region. They also localize the group A A-T gene (ATA) to a region that contains the approximately 850 kb region. They are compatible with linking A-TFresno to 11q22-23. NBS-V2 does not link to this region. Four non-linking families contain only single affecteds, suggesting that these may be spontaneous mutations rather than evidence for an A-T gene outside the 11q22-23 region. Finally, two other non-linking families contain recombinant haplotypes that are compatible with a second A-T gene at 11q22-23, slightly distal to the approximately 850 kb region. However, convincing evidence for a second gene is still lacking.
Adult↗
[Mixed gonadal dysgenesis--a rare cause of primary infertility. Report of 2 cases and review of the literature].
We report on two cases of primary male infertility attributable to mixed gonadal dysgenesis. In one case the diagnosis was made when the patient was 30 years old; in the other, the 44-year-old patient had been evaluated 4 years before for erectile dysfunction, which had been treated with a penile prosthesis without the diagnosis being made. These two cases are life following exceptional in that the diagnosis was made in adult-life following an uncomplicated male adolescence.
Adult↗
Chromosomal breakage, endomitosis, endoreduplication, and hypersensitivity toward radiomimetric and alkylating agents: a possible new autosomal recessive mutation in a girl with craniosynostosis and microcephaly.
A high frequency of spontaneous chromosomal breakage, endomitosis, endoreduplication and hypersensitivity toward both the alkylating agent Trenimon and the radiomimetric drug bleomycin was observed in phytohemagglutinin-stimulated peripheral lymphocytes from a girl with craniosynostosis, microcephaly, ptosis, bird-like facies, and moderate mental retardation. We also observed abnormal chromosomal spiralization and some aspects of abnormal cellular division. Several fruitless attempts were made to establish a cell line. The parents were consanguineous, supporting the existence of a new, rare, autosomal, recessive condition in man. The mutation might involve a gene involved in DNA repair and/or regulation of the mitotic cycle.
Adult↗
Mixed gonadal dysgenesis associated with unilateral cavernosal fibrosis and presenting as a cystic lower abdominal mass.
We report the first case of a patient suffering from mixed gonadal dysgenesis and fibrosis of the left cavernous body. The patient who complained about erectile dysfunction had received a penile prosthesis and was diagnosed 3 years after surgery when internal rudimentary gonads presented as a lower abdominal mass.
Abdominal Neoplasms↗
Partial trisomy 1q, an uncommon chromosomal aberration in erythroleukemia.
A 2 years 4 months old boy with erythroleukemia (FAB-M6) and Down's syndrome is described. Chromosome analysis of bone marrow leukemic blasts revealed apart from the trisomy 21 a partial trisomy of the long arm of chromosome 1:1q23-->1qter in all cells and trisomy 8 mosaicism. To the best of our knowledge this is the first time that a partial trisomy of chromosome 1 in association with erythroleukemia has been described. Previous reports of other hematologic malignancies with aberrations of chromosome 1 indicate that the breakpoint 1q23 is nonrandom and that trisomies of chromosome 1 plays a crucial role in the course of development of hematologic malignancies. This could probably also be true for erythroleukemias.
Child, Preschool↗
Ring Y chromosome: cytogenetic and molecular characterization.
A female patient with Turner syndrome and the karyotype mos45,X/46,X,r(Y)/46,XY is described. Physical mapping of the ring chromosome by Y-specific single-copy and moderately repeated DNA sequences as molecular probes showed that, in addition to the heterochromatic part of Yq, a considerable portion of the Yp has also been lost in the course of the rearrangement. Thus, molecular findings provide independent support that this structurally abnormal sex chromosome is a ring Y and agree with the generally accepted model of ring formation requiring breaks in both chromosome arms. Clinical consequences of Y chromosome mosaicism in patients with Turner syndrome are discussed.
Blotting, Southern↗
Characterisation of a Xp21 microdeletion syndrome in a 2-year-old boy with muscular dystrophy, glycerol kinase deficiency and adrenal hypoplasia congenita.
We report a 2-year-old boy with Duchenne muscular dystrophy (DMD), glycerol kinase deficiency (GK) and adrenal hypoplasia congenita (AHC). At three weeks of age, the patient was hospitalized for the first time with symptoms of hypotone dehydration because of AHC. At present, he shows severe muscular hypotonia and developmental delay. The patient and his family were referred to us for prenatal diagnosis and carrier testing in the mother of the patient and the mother's sister, respectively. The patient's DNA was examined by Southern blot and polymerase chain reaction analyses, using cDNA and genomic probes within and around the dystrophin (DYS) locus. A deletion was revealed, spanning DXS28, the whole dystrophin locus, DXS84 and DXS148, whereas DXS67, DXS68 (pter) and OTC (cen) were found to be retained. The cytogenetically visible microdeletion was also seen in the patient's mother, but not in the mother's sister or the patient's maternal grandmother. Our findings support the locus order pter-DXS67-DXS68-DXS28-AHC-GK-DMD-cen.
Adrenal Insufficiency↗
Frequency of trisomy 21 in Germany before and after the Chernobyl accident.
For Berlin (West) the rate of trisomy 21 among newborn and all prenatally diagnosed cases can be almost completely recorded, including the maternal age distribution. During the 9-year-period from 1980 and 1988 the average number of trisomy 21 per month was about 2, following a Poisson distribution. A significant increase (P less than 0.01) was observed in January 1987, exactly 9 months after the Chernobyl accident. In a supraregional study based on greater than 30,000 prenatal diagnoses performed in 1986, no significant effect could be observed. However, the highest rates of trisomy 21 were observed in the more heavily contaminated, southern part of Germany. The majority of these fetuses were conceived during the period of greatest radioactive exposure. The data are discussed with respect to the effect of low-dose radiation around the time of conception on the induction of non-disjunction in man.
Abnormalities, Radiation-Induced↗
[Bacteriologic findings before and in transcervical chorionic villi biopsy and their clinical relevance].
Between August 1987 and May 1989, bacteriological examinations of smears from the cervical canal was performed in 358 pregnant women, who underwent transcervical sampling of chorionic villi. The outcome of 349 of these pregnancies is documented. 12 of these patients (3.5%) had an artificial abortion for genetic reasons. In 12 other patients, the pregnancy ended before 28 weeks (one child surviving). Microbiological examinations showed that in 187 women (52%), it was possible to culture one or more microorganisms from the cervical canal. The most frequently detected pathogen was Chlamydia trachomatis (111 women, 31%). In pregnancies, where more than one microorganism could be cultured, the risk of following abortion was 8.9 times higher than in those, where no pathogens could be found. In only two of the 12 women with a subsequent spontaneous abortion (16.6%), no microorganism could be found. The bacterial contamination of the cervical canal during TC-CVS seems to be a risk factor for subsequent abortion. Therefore, a bacteriological examination of cervical flora should be performed before as well as during TC-CVS, and antibiotic therapy should be initiated in case of positive results.
Abortion, Septic↗
[Experiences with transcervical chorionic villi biopsy in 274 studies].
In the years 1985-1987, 274 transcervical chorionic villi biopsy samples were taken at the Klinikum Steglitz Medical Center of the Free University of Berlin. We have information on the outcome of 264 pregnancies (96.3%). 229 cases (83.6%) yielded diagnostically usable results. Multiple biopsy samples were taken in 59 (21.5%) cases. Abnormal results were found in 14 patients. Pregnancy was terminated in 6 cases (2.2%) for proven chromosomal aberrations. In two others, spontaneous abortion occurred before the intended induced abortion. In 4 cases of mosaics, amniocentesis was performed subsequently in the 16th week of pregnancy; three of those pregnancies were carried to full term, and the children are healthy. In one case, we saw a spontaneous abortion in the 26th week of pregnancy. In two cases, we found balanced translocations. Miscarriage was observed in 16 CVS patients (5.8%). Abortion was febrile in two cases, septic in two others.
Chorionic Villi Sampling↗
Calla-positive acute leukaemia with t(5q;14q) translocation and hypereosinophilia--a unique entity?
A patient with common acute lymphoblastic leukaemia (ALL), hypereosinophilic syndrome and t(5;14) (q31.1;q32.3) translocation is described. Even with intensive treatment only short periods of complete remission were achieved. Recurrence of the leukaemia was always accompanied by the appearance of eosinophilic granulocytes in the blood and in the bone marrow. Although there is no experimental proof we assume that the hypereosinophilic syndrome is causally related to the chromosome aberration. Translocation of the GM-CSF gene from chromosome No. 5 to chromosome No. 14, might have led to the deregulation of the gene by enhancer sequences of the immunoglobulin heavy-chain region on chromosome No. 14, with the consequence of an overproduction of neutrophilic and particularly eosinophilic granulocytes. Furthermore, stimulation of the leukaemic cell clone may have occurred by this translocation. The similarity of the clinical course with cases described in the literature suggests that this condition is a unique entity of ALL.
Child↗
Trisomy 14 mosaicism leading to cytogenetic discrepancies in chorionic villi sampled at different times.
Short- and long-term cultures of chorionic villi obtained in the 11th week of pregnancy revealed trisomy 14. After induced abortion trisomy 14 mosaicism was established in fetal skin and umbilical cord tissue while a second long-term culture of chorionic villi exhibited a normal karyotype. The results of the pathological investigations are discussed with respect to the cytogenetic findings.
Abortion, Induced↗
A new chromosomal instability disorder confirmed by complementation studies.
Two sisters with a complex clinical pattern, including microcephaly, microgenia, defects of skin pigmentation, anal stenosis/atresia, and combined immunodeficiency together with spontaneous chromosomal instability and cellular hypersensitivity to X-rays and bleomycin are described. Complementation studies on heterokaryons proved that the underlying genetic defect is non-allelic with that of patients with ataxia telangiectasia (complementation groups AB-E) and the Nijmegen breakage syndrome, but identical with the case described by Conley et al. (1986).
Ataxia Telangiectasia↗