Cases reported "Chromosome Deletion"

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1/4. The role of mitochondrial-mediated apoptosis in a myelodysplastic syndrome secondary to congenital deletion of the short arm of chromosome 4.

    OBJECTIVE: myelodysplastic syndromes (MDS) are characterized by peripheral cytopenia and ineffective hematopoiesis. In adult-onset MDS and in certain inherited marrow failure syndromes, apoptosis is increased and is mediated mainly through activation of the Fas pathway. It is unclear whether the various myelodysplastic disorders share the same apoptosis pathways. I investigated apoptosis pathways in a patient with refractory cytopenia with ring sideroblasts associated with congenital 4p deletion to determine the mechanism for bone marrow failure. methods: Marrow cells and lymphoblast cell lines generated from peripheral blood were analyzed for apoptosis and protein expression by flow cytometry, Western blot, and confocal microscopy, either directly or after gamma irradiation (15 G). Cell viability after treatment with inhibitors of specific apoptosis pathways was also determined. RESULTS: Compared to controls, the patient's marrow and lymphoblastoid cells showed significantly higher apoptosis rates and activation of caspase-3. Investigation of the mitochondrial apoptosis pathway showed a consistent pro-apoptosis profile, namely, upregulation of Bax, Bax-alpha, cytochrome c, and Apaf1, and low bcl-2. Differences between the patient's and the normal cells were further accentuated after irradiation; p53 expression was strikingly higher in the patient only after irradiation. In contrast, Fas and FADD expression on the patient's and the control's cells were comparable. Addition of caspase 3 or caspase 9 inhibitors markedly increased patient cell viablity, but blocking anti-Fas antibody did not. CONCLUSION: The ineffective hematopoiesis in this case is explained by increased apoptosis and is linked to hyperactivation of the mitochondrial cell death machinery and not to the Fas pathway, which might be secondary to an intramitochondrial defect. This information is crucial because the development of anti-apoptotic agents for the treatment of MDS may not be universally efficacious and should target the specific derangement.
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ranking = 1
keywords = apoptosis
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2/4. Congenital club foot with survival of motor neuron 1, telomeric (SMN1) gene deletion.

    A boy with nonreducible bilateral congenital talipes equinovarus had delayed milestones with early-onset generalized hypotonia and muscular weakness. The condition remained stable until he was 8 years old. A slow worsening of motor abilities, with myopathic signs, was observed thereafter. A homozygous deletion of exons 7 and 8 of the survival of motor neuron 1, telomeric (SMN1) gene was found, without neuronal apoptosis inhibitory protein (NAIP) gene deletion, leading to the diagnosis of spinal muscular atrophy. Independent ambulation was lost when he was 13 years old. The occurrence of congenital clubfoot with early onset of neurologic signs, but with a very slowly progressive course, has not been reported in spinal muscular atrophy until now.
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ranking = 0.076923076923077
keywords = apoptosis
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3/4. Increased spontaneous apoptosis in T lymphocytes in DiGeorge anomaly.

    The aim of this study was to determine whether increased apoptosis in peripheral blood lymphocytes plays a role in T cell deficiency associated with DiGeorge anomaly. T cell subsets from a patient with DiGeorge anomaly were examined for the expression of Fas, FasL, Bcl-2 and Bcl-XL at the protein level with monoclonal antibodies, using dual-colour flow cytometry, and at the mRNA level in mononuclear cells by quantitative reverse transcriptase-polymerase chain reaction. in vitro spontaneous apoptosis was examined by propidium iodide staining and dna fragmentation, using flow cytometry and gel electrophoresis, respectively. Fas and FasL expression, both at the level of protein and of mRNA, was increased, whereas Bcl-2 expression was decreased both at the level of protein and of mRNA. However, no difference in Bcl-XL expression was observed between the patient and an age-matched control. A significant proportion of both CD4 and CD8 T cells from the patients underwent spontaneous apoptosis, whereas almost no spontaneous apoptosis was observed in the age-matched control. These data suggest that spontaneous apoptosis in T lymphocytes, at least in part, may be responsible for T cell deficiency in DiGeorge anomaly.
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ranking = 0.69230769230769
keywords = apoptosis
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4/4. Axonal neuropathy and predominance of type II myofibers in infantile spinal muscular atrophy.

    Two affected siblings with infantile spinal muscular atrophy (SMA I) presented with generalized muscular hypotonia, which progressed to early death. Quadriceps muscle biopsy did not show the typical neurogenic pattern of spinal muscular atrophy. The histochemical fiber type determination revealed a predominance of type II fibers without type I hypertrophy, an unprecedented finding in spinal muscular atrophy. sural nerve biopsy exhibited findings typical for axonal neuropathy. In one patient, electrical stimulation of peripheral nerves showed an inexcitability of motor and sensory nerves. Genetic studies revealed homozygous deletions of the telomeric survival motor neuron (SMN) gene and the neuronal apoptosis inhibitory protein (NAIP) gene in the affected children. This is the second case report of molecular genetically proven spinal muscular atrophy associated with axonal neuropathy. We conclude atypical findings on muscle biopsy and evidence of axonal neuropathy are compatible with the diagnosis of infantile spinal muscular atrophy.
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ranking = 0.076923076923077
keywords = apoptosis
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