Tetrasomy 21 due to a de novo Robertsonian translocation t(14;21) and an additional free trisomy 21

2001 ◽  
Vol 60 (1) ◽  
pp. 83-85 ◽  
Author(s):  
T Liehr ◽  
V Beensen ◽  
H Starke ◽  
R Hauschild ◽  
E Hempell ◽  
...  
Keyword(s):  
Trisomy 21 ◽  
Robertsonian Translocation ◽  
De Novo

scholarly journals A Rare De Novo Robertsonian Translocation t(21q; 21q) in an Iranian Child With Down Syndrome: A Case Report

2020 ◽  
Author(s):  
Ali Nikfar ◽  
Mojdeh Mansouri ◽  
Gita Fatemi Abhari
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Robertsonian Translocation ◽  
De Novo ◽  
Genetic Disorder ◽  
Female Child ◽  
Medical Sciences ◽  
Nasal Bridge ◽  
Flat Nasal Bridge ◽  
Iranian Child

Down syndrome or trisomy 21 is the most common genetic disorder with a prevalence of 1 in 700 live-born infants. It is characterized by the intellectual disability of varying range, developmental delay, distinctive facial features and various physical abnormalities. The most frequent clinical features include hypotonia, short stature, short neck, upward slanting eyes, flat nasal bridge, bulging tongue, small ears and a single palmar crease of the hands. Mainly there are three cytogenetic forms of Down syndrome including free trisomy 21, mosaicism and Robertsonian translocation. We describe the case of a 1-year-old Iranian female child who presented to our genetic counseling center with intellectual and physical disabilities. The most common features of Down syndrome were present. The cytogenetic analysis confirmed the diagnosis, with detection of the Robertsonian translocation t(21q; 21q). The patient's parents were found to be both phenotypically and cytogenetically normal, so the identified Robertsonian translocation t(21q; 21q) probably have arisen de novo. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(8):522-524.

RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3735-3741 ◽  
Author(s):  
Catherine Roche-Lestienne ◽  
Lauréline Deluche ◽  
Sélim Corm ◽  
Isabelle Tigaud ◽  
Sami Joha ◽  
...  
Keyword(s):  
Dna Binding ◽  
High Frequency ◽  
Trisomy 21 ◽  
De Novo ◽  
Blast Crisis ◽  
Clonal Evolution ◽  
Chronic Phase ◽  
Chromosome 21 ◽  
Imatinib Resistance ◽  
Molecular Abnormalities

Abstract Acquired molecular abnormalities (mutations or chromosomal translocations) of the RUNX1 transcription factor gene are frequent in acute myeloblastic leukemias (AMLs) and in therapy-related myelodysplastic syndromes, but rarely in acute lymphoblastic leukemias (ALLs) and chronic myelogenous leukemias (CMLs). Among 18 BCR-ABL+ leukemias presenting acquired trisomy of chromosome 21, we report a high frequency (33%) of recurrent point mutations (4 in myeloid blast crisis [BC] CML and one in chronic phase CML) within the DNA-binding region of RUNX1. We did not found any mutation in de novo BCR-ABL+ ALLs or lymphoid BC CML. Emergence of the RUNX1 mutations was detected at diagnosis or before the acquisition of trisomy 21 during disease progression. In addition, we also report a high frequency of cryptic chromosomal RUNX1 translocation to a novel recently described gene partner, PRDM16 on chromosome 1p36, for 3 (21.4%) of 14 investigated patients: 2 myeloid BC CMLs and, for the first time, 1 therapy-related BCR-ABL+ ALL. Two patients presented both RUNX1 mutations and RUNX1-PRDM16 fusion. These events are associated with a short survival and support the concept of a cooperative effect of BCR-ABL with molecular RUNX1 abnormalities on the differentiation arrest phenotype observed during progression of CML and in BCR-ABL+ ALL.

A Case of Angelman Syndrome Arising as a Result of a De Novo Robertsonian Translocation

1996 ◽  
Vol 45 (1-2) ◽  
pp. 255-261 ◽  
Author(s):  
S. Ramsden ◽  
L. Gaunt ◽  
A. Seres-Santamaria ◽  
J. Clayton-Smith
Keyword(s):  
Angelman Syndrome ◽  
Robertsonian Translocation ◽  
De Novo ◽  
Uniparental Disomy ◽  
Male Child ◽  
Paternal Uniparental Disomy

AbstractA male child has been identified with Angelman syndrome. He has been shown to carry a de novo Robertsonian 15/15 translocation where both chromosome 15s have been derived from the father. Consequently the disease in this instance is due to paternal uniparental disomy.

De Novo COL7A1 mutation in a patient with trisomy 21: coexistence of dystrophic epidermolysis bullosa and Down syndrome

2012 ◽  
Vol 51 (9) ◽  
pp. 1078-1081
Author(s):  
Javiera A. Catalán ◽  
Fernando A. Rodríguez ◽  
María J. Yubero ◽  
Francis Palisson ◽  
María J. Gana ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Epidermolysis Bullosa ◽  
Trisomy 21 ◽  
De Novo ◽  
Dystrophic Epidermolysis Bullosa

RUNX1 DNA-Binding Mutations and RUNX1-PRDM16 Cryptic Fusion in BCR/ABL+ Leukemias Are Frequently Associated with Secondary Trisomy 21 and May Contribute to Clonal Evolution and Imatinib Resistance.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2786-2786
Author(s):  
Catherine Roche-Lestienne ◽  
Laureline Deluche ◽  
Selim Corm ◽  
Isabelle Tigaud ◽  
Sami Joha ◽  
...  
Keyword(s):  
Dna Binding ◽  
Disease Progression ◽  
High Frequency ◽  
Trisomy 21 ◽  
De Novo ◽  
Point Mutations ◽  
Imatinib Resistance ◽  
Exon 2 ◽  
Molecular Abnormalities ◽  
Recurrent Mutations

Abstract Background: Besides the extensively studied point mutations in the BCR/ABL TK domain as the clinically most important cause of imatinib (IM) resistance either in CML and Philadelphia-positive (Ph+) ALL, additional acquired genetic events contributing to resistance/disease progression are not fully understood. Many evidences suggest that the enhanced survival and differentiation arrest of the CML blast crisis (BC) cells depends on the cooperation of BCR/ABL with other genes deregulated during disease progression. A recent study has identified RUNX1/AML1 transcription factor gene as a modulator of the cellular response towards IM in vitro and in vivo in mice, suggesting its possible involvement in disease persistence in IM-resistant CML patients. Purpose: We investigated RUNX1 molecular abnormalities (point mutations or cryptic chromosomal RUNX1 translocation to a novel recently described gene partner PRDM16 at 1p36) in 18 Ph+ leukemias. The observation that RUNX1 mutated allele is frequently duplicated by acquired trisomy of the altered chromosome 21 in acute myeloblastic leukemias (AML) prompt us to focus our analysis on a selected cohort (1 CP-CML, 3 AP-CML, 8 myeloid BC, 1 lymphoid BC, 2 de novo Ph+ ALL-B, 1 de novo AML and 1 therapy-related- Ph+ ALL) presenting acquired trisomy 21 along disease course. Methods: From peripheral blood leucocytes, recurrent mutations were investigated by sequencing DNA PCR fragments corresponding to exon 3 to 8 of RUNX1. RUNX1-PRDM16 fusion was investigated by RT-PCR (i.e. RUNX1 exon 5-PRDM16 exon 2 junction) and by FISH using the TEL/AML1 dual color/dual fusion translocation probes (Vysis, Downer’s grove, IL, USA). Results: We report a high frequency (33%) of recurrent point mutations (4 in myeloid BC CML and 1 in CP-CML) within the DNA-binding region of RUNX1. We did not find any mutation in de novo BCR/ABL+ ALLs or lymphoid BC CMLs. Onset of RUNX1 mutations was detected at diagnosis or before the acquisition of trisomy 21. We also report a high frequency of RUNX1-PRDM16 fusion for 3 out of 7 investigated patients: 2 CMLs and, for the first time reported to our knowledge, 1 therapy-related BCR/ABL+ ALL. RUNX1-PRDM16 is probably transcribed at low levels since only few bone marrow metaphases with trisomy 21 were t(1;21)(p36;q22) positive. Two patients presented both RUNX1 mutations and RUNX1-PRDM16 fusion. All these events are associated with a poor survival: 14 out of 18 patients died with a median survival of 3 months after the diagnosis of the acquired clonal trisomy 21. Furthermore, none of the patients in our study raised durable optimal responses to IM. Conclusion: Our data support the concept of a cooperative effect of BCR/ABL with molecular RUNX1 abnormalities on the differentiation arrest phenotype observed during progression of CML and in BCR/ABL+ ALL. Our findings also support that it may exist a heterogeneous genetic status at diagnosis of CML, underlying the need of further investigations able to define more precisely the molecular disease characteristics at diagnosis for better therapeutic decision adjustments.

High Frequency of AML1/RUNX1 Mutations in Specific Cytogenetic Subgroups in De Novo Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 986-986
Author(s):  
Frank Dicker ◽  
Claudia Haferlach ◽  
Wolfgang Kern ◽  
Torsten Haferlach ◽  
Susanne Schnittger
Keyword(s):  
Trisomy 21 ◽  
De Novo ◽  
Normal Karyotype ◽  
Clinical History ◽  
Trisomy 13 ◽  
Complex Karyotype ◽  
Trisomy 8 ◽  
Cytogenetic Aberrations ◽  
De Novo Aml ◽  
Acute Myeloid

Somatic mutations in the DNA-binding domain, the socalled Runt homology domain, of the AML1/RUNX1 gene have been identified to occur in acute myeloid leukaemia (AML) with the highest incidence in AML M0, in therapy-related myelodysplastic syndrome (t-MDS), in therapy-related AML (t-AML) and AML after MDS (s-AML). Cytogenetic aberrations that are associated with RUNX1 mutations (RUNX1mut) have been reported to be trisomy 13 in AML and trisomy 21 in myeloid malignancies, but also loss of chromosome 7q, mainly in t-MDS but rarely in t-AML. So far the majority of RUNX1mut have been described in secondary or therapy-related cases. Thus, we characterized a cohort of 119 patients (pts) with de novo AML and compared these results to 19 MDS and s-AML, 2 t-MDS (n=2) and 8 t-AML. The cohort was selected for specific cytogenetics with high reported frequencies of RUNX1mut: trisomy 13 (n=17), trisomy 21 (n=9), −7/7q- (n=34). In addition pts with normal karyotype (NK) (n=42), inv(3)/t(3;3) (n=12), trisomy 8 (n=11), complex karyotype (n=13) and 10 pts with various other cytogenetic aberrations (other) were analyzed. The incidence of RUNX1mut in the different cytogenetic subgroups was: 94% (16/17) in +13, 56% (5/9) in +21, 29% (10/34) in −7/7q-, 10% (4/42) in NK, 17% (2/12) in inv(3)/t(3;3), 18% (2/11) in +8, 0% (0/13) in complex karyotype and 20% (2/10) in other, respectively. Based on clinical history we observed RUNX1 mutations in: 6/19 (32%) in MDS/s-AML, 1/10 (10%) in t-MDS/t-AML and 34/119 (29%) in de novo AML. Of the 6 RUNXmut cases with MDS/s-AML the karyotypes were heterogeneous NK (n=1), −7 (n=2) +13 (n=1), +21 (n=1), and inv(3) (n=1). The only recurrent cytogenetic aberration in MDS/s-AML was −7, thus the frequency of RUNXmut in the MDS/s-AML group with −7 was 2/8 (25%). Also the only RUNX1mut case with t-AML revealed a −7. These data correspond to those reported in the literature. We further focussed on the analyses of RUNX1 in de novo AML which is rarely reported so far. In the de novo AML group only we detected RUNX1mut with the highest frequency in +13 (16/16; 100%) followed by +21 (4/8; 50%) −7 (7/21; 33%), + 8 (2/10, 20%), inv(3) (1/8; 12.5%), and NK (3/33; 9.1%). In addition, in the group with “other” aberration 2/8 were mutated. Interestingly, these 2 mutated cases displayed a high number of trisomies including +8 and +13. No RUNX1mut were detected in AML with complex karyotype (n=10). These data for the first time show that RUNX1mut are not strongly correlated to MDS, s-AML or t-AML. With almost the same frequency they can be observed in de novo AML if specific cytogenetic groups are considered. Thus the RUNXmut seem to be more related to these cytogenetic subgroups than to the MDS, s-AML or t-AML.

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