1/51. Familial cerebellar hypoplasia and pancytopenia without chromosomal breakages.Two siblings manifested a neuro-haematologic syndrome characterised by low birth weight, failure to thrive, chronic persistent tongue ulceration, severe truncal ataxia and pancytopenia without either telangiectasia or chromosomal instability. One sibling died from sepsis and the cerebellum demonstrated reduced cellularity of the molecular and granular layers with relative preservation of purkinje cells and minimal gliosis. A surviving sibling has shown haematologic progression to a myelodysplastic disorder. There was no evidence of any chromosomal instability following exposure of fibroblasts and lymphocytes to irradiation. monosomy-7 was not present in the surviving sibling. We suspect that these two patients represent another example of the rare Hoyeraal-Hreidarsson syndrome and we are currently engaged in very close monitoring of the surviving sibling for evidence of any karyotypic abnormality.- - - - - - - - - - ranking = 1keywords = breakage (Clic here for more details about this article) |
2/51. Ataxia, ocular telangiectasia, chromosome instability, and Langerhans cell histiocytosis in a patient with an unknown breakage syndrome.An 8 year old boy who had Langerhans cell histiocytosis when he was 15 months old showed psychomotor regression from the age of 2 years. microcephaly, severe growth deficiency, and ocular telangiectasia were also evident. Magnetic nuclear resonance imaging showed cerebellar atrophy. Alphafetoprotein was increased. Chromosome instability after x irradiation and rearrangements involving chromosome 7 were found. Molecular study failed to show mutations involving the ataxia-telangiectasia gene. This patient has a clinical picture which is difficult to relate to a known breakage syndrome. Also, the relationship between the clinical phenotype and histiocytosis is unclear.- - - - - - - - - - ranking = 14.178119694404keywords = breakage syndrome, breakage (Clic here for more details about this article) |
3/51. Normal expression of the fanconi anemia proteins FAA and FAC and sensitivity to mitomycin C in two patients with Seckel syndrome.Seckel syndrome is a rare autosomal recessive disorder. The classical presentation includes pre- and postnatal growth deficiency, mental retardation, and characteristic facial appearance. There have been several reports of associated hematological abnormalities and chromosomal breakage, findings suggestive of fanconi anemia (FA). We tested for these findings in two Arabic patients with this syndrome. We compared the growth profile of lymphoblastoid cells from our patients and their parents with the FA group A cell line HSC72 in the presence and absence of mitomycin C (MMC). By Western analysis, we also determined the expression of FAA and FAC, two FA disease gene products that together account for approximately 80% of FA. Unlike HSC72 cells, cells from the patients were resistant to MMC, and both FAA and FAC proteins were expressed at similar levels in all cell lines. There is an increasing recognition of clinical variability and perhaps genetic heterogeneity in Seckel syndrome. Our results demonstrate that cross-link sensitivity comparable to FA is not a uniform finding in patients with Seckel syndrome.- - - - - - - - - - ranking = 0.25keywords = breakage (Clic here for more details about this article) |
4/51. nijmegen breakage syndrome-associated T-cell-rich B-cell lymphoma: case report.In 1981 Weemaes et al. first described the nijmegen breakage syndrome (NBS), a rare autosomal recessive disorder characterized by stunted growth, microcephaly, immunodeficiency, spontaneous chromosome instability, and a peculiar predisposition to cancer development. Most NBS-related malignancies are lymphomas, but their pathologic features have rarely been specified. We report here the case of a northern Italian 8-year-old child who, 2 years after the diagnosis of NBS, developed a diffuse large B-cell lymphoma (T cell-rich B-cell lymphoma variant). The histological and immunobiological features of the lymphoma population are analyzed and discussed in detail.- - - - - - - - - - ranking = 14.178119694404keywords = breakage syndrome, breakage (Clic here for more details about this article) |
5/51. Embryonal rhabdomyosarcoma and chromosomal breakage in a newborn infant with possible Dubowitz syndrome.We report on a newborn girl with Dubowitz syndrome (DS) and embryonal rhabdomyosarcoma (ERMS), with multiple chromosomal breakage (MCB). The tumor was resected but recurred in a few months, resulting in the infant's death. Malignancy and chromosomal breakage have been reported previously in DS. However, ERMS has not been reported among the malignant tumors diagnosed in DS. To our knowledge, concurrence of DS, ERMS, and MCB has not been reported previously. This is the first observation of DS in the Arab ethnic group.- - - - - - - - - - ranking = 1.5keywords = breakage (Clic here for more details about this article) |
6/51. nijmegen breakage syndrome. The International nijmegen breakage syndrome Study Group.BACKGROUND: nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder. NBS-1, the gene defective in NBS, is located on chromosome 8q21 and has recently been cloned. The gene product, nibrin, is a novel protein, which is member of the hMre11/hRad50 protein complex, suggesting that the gene is involved in DNA double strand break repair. AIMS: To study the clinical and laboratory features of NBS as well as the genotype-phenotype relation. methods: Fifty five patients with NBS, included in the NBS registry in Nijmegen were evaluated. The majority of the patients were of eastern European ancestry. Most of them had shown a truncating 5 bp deletion 657-661 delACAAA. Four further truncating mutations have been identified in patients with other distinct haplotypes. RESULTS AND CONCLUSIONS: Essential features found in NBS were microcephaly, usually without severe retardation, typical facial appearance, immunodeficiency, chromosomal instability, x ray hypersensitivity, and predisposition to malignancy. In 40% of the patients cancer was noted before the age of 21 years. Important additional features were skin abnormalities, particularly cafe au lait spots and vitiligo, and congenital malformations, particularly clinodactyly and syndactyly. Congenital malformations, immunodeficiency, radiation hypersensitivity, and cancer predisposition were comprehensible in case of dysfunctioning of dna repair mechanisms. No specific genotype-phenotype relation could be found. patients with the same genotype may show different phenotypes and patients with different genotypes may express the same phenotype. Specific mutations did not lead to specific clinical features.- - - - - - - - - - ranking = 14.178119694404keywords = breakage syndrome, breakage (Clic here for more details about this article) |
7/51. telomere-telomere (end to end) fusion of chromosomes 7 and 22 with an interstitial deletion of chromosome 7p11.2-->p15.1: phenotypic consequences and possible mechanisms.We report a rare case of a de novo end to end fusion of chromosomes 7 and 22 in conjunction with an interstitial deletion of chromosome 7p11.2p15.1 in a newborn with congenital anomalies. The proband presented for chromosome analysis with bilateral cataracts, dysmorphic facies and distal limb abnormalities. Chromosome analysis showed a 45,XY,der(22)psu dic(22;7)(p13;p22.3)del(7)(p11.2p15.1) karyotype. This short arm to short arm fusion of chromosomes 7 and 22 resulted in a pseudodicentric chromosome. The interstitial deletion in the short arm of chromosome 7 was likely a result of breakage and reunion related to instability of the dicentric chromosome. Loss of genetic material in this region of chromosome 7p has been implicated in the pathophysiology of craniosynostosis and cephalopolysyndactyly syndromes.- - - - - - - - - - ranking = 0.25keywords = breakage (Clic here for more details about this article) |
8/51. Japanese family with an autosomal dominant chromosome instability syndrome: a new neurodegenerative disease?We report on a Japanese family having an autosomal dominant neurodegenerative disease with chromosomal instability and radiosensitivity. Clinical manifestations of affected members included short stature, osteoporosis, severe dental caries, and various neurological abnormalities, such as mental retardation, depression, dysarthria, hyperreflexia, and ataxic gait. MRI demonstrated a markedly atrophic spinal cord and degeneration of the white matter. Cytogenetic examination showed spontaneous chromosome rearrangements at 14q11.2 and hypersensitivity to radiation and bleomycin. The degree of these cytogenetic abnormalities was significantly higher in the patients than in normal controls but lower than in patients with ataxia telangiectasia or nijmegen breakage syndrome. Moreover, genetic anticipation was observed in this family: the age of disease onset became earlier, MRI abnormalities more extensive, and the chromosome hypersensitivity to radiation increased in successive generations. We speculate that a basic defect in this family is a mutation in the gene that is responsible for DNA double-strand breakage repair.- - - - - - - - - - ranking = 3.0856239388809keywords = breakage syndrome, breakage (Clic here for more details about this article) |
9/51. Isochromosome (7)(q10) in Shwachman syndrome without MDS/AML and role of chromosome 7 anomalies in myeloproliferative disorders.Shwachman syndrome (SS) is an autosomal recessive disorder in which bone marrow dysfunction is observed, with development of myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML) in up to one third of the cases. Inconclusive data are available as to increased chromosome breakage in SS, while chromosome 7 anomalies, and often an isochromosome (7)(q10), are frequent in cases with MDS/AML. We report on the consistent presence of an i(7)(q10) in the bone marrow and blood lymphocytes in one of two sisters affected with SS without any clinical or cytological signs of MDS/AML. Thus, this patient was either a case of constitutional mosaicism for the i(7)(q10), or this had to be acquired in a nondysplastic and non-neoplastic marrow clone. DNA polymorphism analysis demonstrated the paternal origin of the i(7q). We postulate that the SS mutation acts as a mutator gene, and causes karyotype instability; abnormal clones would thus arise in the marrow, and chromosome 7 anomalies, i(7q) in particular, will in turn lead to MDS/AML. If this interpretation is correct, it would be also an indication to consider chromosome 7 anomalies in general, out of SS, as primary changes in MDS/AML pathogenesis.- - - - - - - - - - ranking = 0.25keywords = breakage (Clic here for more details about this article) |
10/51. role of nijmegen breakage syndrome protein in specific T-lymphocyte activation pathways.nijmegen breakage syndrome (NBS) is a genetic disorder characterized by immunodeficiency, microcephaly, and "bird-like" facies. NBS shares some clinical features with ataxia telangiectasia (AT), including increased sensitivity to ionizing radiation, increased spontaneous and induced chromosome fragility, and strong predisposition to lymphoid cancers. The mutated gene that results in NBS codes for a novel double-stranded DNA break repair protein, named nibrin. In the present work, a Spanish NBS patient was extensively characterized at the immunological and the molecular DNA levels. He showed low CD3( )-cell numbers and an abnormal low CD4( ) naive cell/CD4( ) memory cell ratio, previously described in AT patients and also described in the present report in the NBS patient. The proliferative response of peripheral blood lymphocytes in vitro to mitogens is deficient in NBS patients, but the possible link among NBS mutations and the abnormal immune response is still unknown.- - - - - - - - - - ranking = 14.178119694404keywords = breakage syndrome, breakage (Clic here for more details about this article) |
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