Biclonal myelodysplastic syndrome involving six chromosomes and monoallelic loss of RB1 - A rare case

<p>Abstract</p> <p>Background</p> <p>Myelodysplastic syndrome (MDS) represents a group of clonal hematological disorders characterized by progressive cytopenia, and reflects to defects in erythroid, myeloid and megakaryocytic maturation. MDS is more frequently observed in older aged patients with cytogenetic abnormalities like monosomy of chromosome(s) 5 and/or 7. In 50% of de novo MDS cases, chromosomal aberrations are found and rearrangements involving the retinoblastoma (<it>RB1</it>) gene in 13q14 are found.</p> <p>Results</p> <p>Here, we are presenting a case report of a rare biclonal MDS with a karyotype of 45, XY,-4, der(6)t(4;6)(p15.1;p21.3), der(8)t(4;8)(q31.2;q22), t(13;16)(q21.3;p11.2)<abbrgrp><abbr bid="B11">11</abbr></abbrgrp>/45, XY, der(7)t(7;13)(p22.2~22.3;q21.3),-13 <abbrgrp><abbr bid="B9">9</abbr></abbrgrp>. The patient was diagnosed according to WHO classification as refractory anemia with excess of blasts (RAEB-II).</p> <p>Immunophenotyping was positive for CD11b, CD11c, CD10, CD13, CD15, CD16 and CD33.</p> <p>Conclusion</p> <p>We report, a novel and cytogenetically rare case of a biclonal MDS with complex chromosomal aberrations and deletion of <it>RB1</it>-gene in both clones. These findings are associated with a poor prognosis as the patient died 3 months after diagnosis.</p

Partial trisomy 9p22 to 9p24.2 in combination with partial monosomy 9pter in a Syrian girl

<p>Abstract</p> <p>Background</p> <p>Partial trisomy of the short arm of chromosome 9 is among the most common autosomal structural chromosomal anomalies leading to chromosomal imbalance in human. Clinical characteristics are craniofacial dysmorphism including hypertelorism, prominent nose, deep-set eyes, and down-slanting palpebral fissures. The degree of clinical severity in partial trisomy 9p roughly correlates with the size of the chromosomal imbalance. Therefore, breakpoints as well as clinical findings need to be precisely defined for differential diagnosis.</p> <p>Results</p> <p>Chromosomes of a young female were analyzed due to primary amenorrhea, short stature, developmental delay and a characteristic facial appearance. Cytogenetic analysis using GTG banding identified a karyotype 46, XX, add(9pter). Surprisingly the application of high resolution molecular cytogenetic techniques characterized a partial trisomy 9p24.2-p22 and partial monosomy 9pter-p24.2. To the best of our knowledge only four similar case were reported by now.</p> <p>Conclusion</p> <p>Attempts for genotype-phenotype correlations for partial trisomy 9p might have been hampered by the fact that more complex, cryptic aberrations were neither considered nor detected in comparable clinical cases.</p

A rare case of chronic myeloid leukemia with secondary chromosomal changes including partial trisomy 17q21 to 17qter and partial monosomy of 16p13.3

<p>Abstract</p> <p>Background</p> <p>The so-called Philadelphia (Ph) chromosome is present in almost all cases with chronic myeloid leukemia (CML). Around 5-10% of these patients show complex translocations involving other chromosomes in addition to and/or besides chromosomes 9 and 22. As nowadays most CML cases are treated with Imatinib, variant rearrangements have in general no specific prognostic significance, though events of therapy resistance remain to be studied.</p> <p>Results</p> <p>Here we report a Ph chromosome positive patient with hematological typical chronic phase CML. Untypically, an unbalanced complex rearrangement involving chromosomes 16 and 17 leading to a deletion of 16pter and partial trisomy of 17q21 to 17qter, was identified besides a trisomy 8 and an additional Ph chromosome in a part of malignant cells.</p> <p>Conclusion</p> <p>Here a novel and cytogenetically unique case of a Ph chromosome positive CML clinically in chronic phase is reported, having complex secondary chromosomal aberrations. Thus, CML patients with complex chromosomal changes are nonetheless treatable by Imatinib.</p

Novel complex translocation involving 5 different chromosomes in a chronic myeloid leukemia with Philadelphia chromosome: a case report

<p>Abstract</p> <p>Background</p> <p>The well-known typical fusion gene BCR/ABL can be observed in connection with a complex translocation event in only 2-10% of cases with chronic myeloid leukemia (CML). As currently most CML cases are treated with Imatinib, variant rearrangements have in general no specific prognostic significance, though the emergence of therapy resistance remains to be studied.</p> <p>Results</p> <p>Here we report an exceptional CML case with complex chromosomal aberrations not observed before, involving a 5 chromosome translocation implying chromosomal regions such as 1q42, 4p14 and 5q31 besides 9q34 and 22q11.2.</p> <p>Conclusion</p> <p>The reported rearrangement developed most probably in one initial step and had no influence on a good response during Imatinib treatment.</p

Integration of sequence data from a consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2×10-6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted. © 2014 Plenge et al

Contribution a l'etude de la transmission des remaniements chromosomiques radioinduits

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc