Search Results

You are looking at 1 - 4 of 4 items for

  • Author: Adriana Sireteanu x
Clear All Modify Search
Open access

Cristina Rusu, Adriana Sireteanu, Lăcrămioara Butnariu, Monica Pânzaru, Elena Braha, Doina Mihăilă and Roxana Popescu

Abstract

Duchenne and Becker muscular dystrophies (DMD/BMD) are X-linked progressive muscle disorders determined by mutations of the dystrophin (DMD) gene. Multiplex Ligation - Dependent Probe Amplification (MLPA) is a simple, inexpensive and reliable test for molecular diagnosis of DMD gene mutations. It identifies exonic copy number variations in the DMD gene, but the test should be completed with sequencing analysis in case of single exon deletions/duplications. The aim of this study was to evaluate the efficiency of MLPA as a DMD mutation screening tool in affected males and carrier females, as well as to appreciate the frequency of different types of mutations and to check the validity of the “reading frame rule”. We have used MLPA for the detection of deletions/ duplications in DMD gene in 53 individuals (30 affected males and 23 asymptomatic female relatives) referred for evaluation and genetic counseling due to the clinical suspicion of DMD/BMD. In the affected males (21 DMD and 9 BMD) MLPA had a detection rate of 63.5% (53.5% deletions and 10% duplications). The most frequently deleted exon was exon 45 and the most frequent duplication involved exons 3-5, confirming the presence of the two hotspot mutation regions reported in the literature. Mutations detected in our study have a slightly different location compared to literature data. Reading frame rule was valid in 84% of our cases.

Open access

Roxana Popescu, Angela Dăscălescu, Cătălin Dănăilă, Doramina Ghiorghiu, Mihaela Zlei, Anca Ivanov, Adriana Sireteanu, Eusebiu Vlad Gorduza and Doina Azoicăi

Abstract

The coexistence of t(9;22) and inv(16) has been described in a very limited number of cases of CML, de novo or therapy-related AML. We report a patient with CML who presented both inversion of chromosome 16 and Philadelphia chromosome and evolved towards the blast phase under treatment with Imatinib. Laboratory diagnosis and monitoring was made by flow cytometry, conventional cytogenetics and molecular genetics techniques. The inv(16), detected by karyotyping in the Philadelphia chromosome positive clone at the moment of the blast transformation, was retrospectively assessed by means of real-time PCR, and was proved to have been present since diagnosis. The bone marrow biopsy performed in the blast phase of CML confirmed the presence of blasts belonging to the myeloid lineage, with indications of monocytic differentiation, frequently associated with inv(16). Moreover, the case also associated a F359V tyrosine kinase domain mutation, resulting in intermediate resistance to Imatinib and Nilotinib, which imposed therapy-switch to Dasatinib. In our case the evolution was progressive, followed by death due to lack of response to tyrosine kinase inhibitors, 18 months after diagnosis. The coexistence of t(9;22) and inv(16) in CML seems to be associated with an aggressive clinical evolution and resistance to tyrosine kinase inhibitor therapy. Due to the very small number of cases described in literature, therapeutic decisions are still difficult for patients displaying these abnormalities

Open access

Ion Antohe, Angela Dăscălescu, Cătălin Dănăilă, Mihaela Zlei, Iuliu Ivanov, Adriana Sireteanu, Oana Boca, Raluca Oană and Petru Cianga

Abstract

Background: Acute basophilic leukemia is a rare subtype of acute myeloid leukemia, as categorized by the 2008 World Health Organization classification of myeloid neoplasms. Acute basophilic leukemia diagnosis requires thorough morphological, cytochemical, immunophenotypic, molecular, and cytogenetic studies and exclusion of other hematological neoplasms associating basophilia. The disease course is defined by histamine driven, occasionally life-threatening respiratory, cardiovascular, cutaneous or digestive complications, as well as primary refractoriness to standard therapy. Clinical presentation: We herein report a case of a 63-year-old asthmatic female patient diagnosed with acute basophilic leukemia, associated with previously unpublished cytogenetic features and FLT-3 ITD mutation, pulmonary leukostasis and spontaneous pulmonary capillary leak syndrome, which worsened immediately following chemotherapy initiation. Respiratory complications were successfully managed, but recrudesced upon emergence of refractory disease and were ultimately fatal. We highlight the likelihood of pulmonary complications induced by basophil degranulation and tumor lysis in hypercellular acute basophilic leukemia and the potential benefit of histamine receptor blockade in this setting.

Open access

Adriana Sireteanu, Roxana Popescu, Elena Emanuela Braha, Cornel Bujoran, Lăcrămioara Butnariu, Lavinia Caba, Elena Graur, Eusebiu Vlad Gorduza, Mihaela Grămescu, Iuliu Cristian Ivanov, Monica Pânzaru and Cristina Rusu

Abstract

Intellectual disability (ID) is a common disorder, with major consequences for individual, family and society. Due to clinical and genetic heterogeneity of ID, in about 50% of cases an etiologic diagnosis cannot be established. The aim of this study was to evaluate the ability of a combination of MLPA kits to establish the diagnosis in 369 patients with syndromic ID and normal or uncertain routine karyotype results. All patients were assessed for chromosome imbalance using SALSA MLPA P064 or P096 kits, if the phenotype was suggestive of a microdeletion syndrome (subgroup A - 186 patients), or subtelomeric P036 and P070 kits, if the phenotype was not suggestive of a microdeletion syndrome or if the result of the standard karyotype was uncertain (subgroup B - 183 patients). Abnormal results detected by these kits were further characterized using appropriate follow-up MLPA kits (Telomere Follow-up set, P029-A1, P250-B2, ME028-B1). In subgroup A we identified 25 patients with microdeletions (13.4%). Using subtelomere screening and follow-up kits in subgroup B we detected cryptic rearrangements in 7.5% cases and identified the origin of the unknown material noticed in the standard karyotype in 10 out of 11 patients. Summarizing data from the two groups, the combined use of MLPA kits led to the diagnosis in 10.6% (38/358) patients with normal karyotype. Using follow-up MLPA kits allowed us both to confirm abnormalities and to determine their size, which facilitated the interpretation of the clinical significance of these rearrangements. For laboratories that do not have yet access to microarray technology, using several MLPA kits represents an effective strategy for establishing the diagnosis in ID patients.