A Novel Variant Rearrangement of the Rare Aberration dic(17;20)(p11.2;q11.2) Characterized by Array-CGH as an Insertion in a Patient with Myelodysplastic Syndrome of Multilineage Dysplasia (MDS-MLD)

2020 ◽  
Vol 160 (1) ◽  
pp. 22-28
Author(s):  
Maryna A. Vazmitsel ◽  
Vasiliki Grammatopoulou ◽  
Jianhui Yao ◽  
Jacqueline R. Batanian
Keyword(s):  
Myelodysplastic Syndrome ◽  
Array Cgh ◽  
De Novo ◽  
Chromosome Analysis ◽  
Chromosome 17 ◽  
Flat Band ◽  
Derivative Chromosome ◽  
Novel Variant ◽  
Unknown Gene ◽  
First Time

We report on a novel variant of the dicentric chromosome 17;20 (dic (17;20)(p11.2;q11.2) in a patient with de novo myelodysplastic syndrome (MDS). Based on FISH and array-CGH, the variant turns out to be an insertion of chromosome 17 (17p11.2-telomere 17) into chromosome 20 with breakpoints at 20q11.22 and 20q13.33. Based on conventional chromosome analysis and G-banding patterns, the region 17p11.2-17q25 was directly inserted between 20q11.22 and 20q13.33. The breakpoint junctions occurred within KCNJ12 (17p11.2), UQCC1 (20q11.2), and CDH4 (20q13.3), leading to 5′ deletions of all the genes and positioning the 3′ of UQCC1 next to KCNJ12 at 17p11.2 and CDH4 next to an unknown gene at 17q25-20q13.3. In addition, the centromere of chromosome 17 was not active, transforming the primary constriction to a flat band. Therefore, the novel insertion variant is a pseudo dicentric derivative chromosome with one functional centromere: 45,XX,der(17;20)del(20)(q11.22q13.33)ins(20;17)(q11.2;p11.2q25). A review of the literature of all dic(17;20) cases is presented. For the first time, we report an array-CGH characterization of such rare variant that revealed to be an insertion.

scholarly journals Refined chromosome analysis as an independent prognostic indicator in de novo myelodysplastic syndromes

Blood ◽  
1986 ◽  
Vol 67 (6) ◽  
pp. 1721-1730
Author(s):  
JJ Yunis ◽  
RE Rydell ◽  
MM Oken ◽  
MA Arnesen ◽  
MG Mayer ◽  
...  
Keyword(s):  
Median Survival ◽  
Myelodysplastic Syndromes ◽  
De Novo ◽  
Chromosome Analysis ◽  
Prognostic Indicator ◽  
Partial Loss ◽  
Monosomy 7 ◽  
Single Chromosome ◽  
Wide Range ◽  
First Time

In a study of 56 consecutive adult patients with de novo myelodysplastic syndromes (MDS), all cases were successfully analyzed with two refined chromosome banding techniques. Most patients (44 of 56, 79%) were found to have a chromosome defect. The majority of these patients had a recurrent loss of chromosomal material rather than a reciprocal translocation or inversion, as commonly found in acute leukemia. The three largest chromosomal categories found were associated with a wide range of survival. Twelve patients (21%) had normal chromosomes, a stable clinical course, and long survival (median follow-up time of 49 months, with all patients alive). Nine patients had in common a single chromosome defect resulting in either monosomy 7 or deletion 7q. They had a median survival of 12 months, and four died of acute nonlymphocytic leukemia (ANLL). Of 12 patients with complex defects, 11 had a complete or partial loss of a chromosome 5 and a complete or partial loss of the long arm of a chromosome 7 or 20. They had a poor median survival of four months, and six patients died of ANLL. Although the French-American-British (FAB) classification was also found to have some prognostic value, FAB subgroups were chromosomally heterogeneous and showed less dramatic differences in median survival than the larger chromosomal subgroups. We have shown, for the first time, that a refined chromosomal analysis is an independent prognostic indicator in de novo MDS and may be helpful in establishing therapeutic approaches in this difficult group of heterogeneous disorders.

scholarly journals Refined chromosome analysis as an independent prognostic indicator in de novo myelodysplastic syndromes

Blood ◽  
1986 ◽  
Vol 67 (6) ◽  
pp. 1721-1730 ◽  
Author(s):  
JJ Yunis ◽  
RE Rydell ◽  
MM Oken ◽  
MA Arnesen ◽  
MG Mayer ◽  
...  
Keyword(s):  
Median Survival ◽  
Myelodysplastic Syndromes ◽  
De Novo ◽  
Chromosome Analysis ◽  
Prognostic Indicator ◽  
Partial Loss ◽  
Monosomy 7 ◽  
Single Chromosome ◽  
Wide Range ◽  
First Time

Abstract In a study of 56 consecutive adult patients with de novo myelodysplastic syndromes (MDS), all cases were successfully analyzed with two refined chromosome banding techniques. Most patients (44 of 56, 79%) were found to have a chromosome defect. The majority of these patients had a recurrent loss of chromosomal material rather than a reciprocal translocation or inversion, as commonly found in acute leukemia. The three largest chromosomal categories found were associated with a wide range of survival. Twelve patients (21%) had normal chromosomes, a stable clinical course, and long survival (median follow-up time of 49 months, with all patients alive). Nine patients had in common a single chromosome defect resulting in either monosomy 7 or deletion 7q. They had a median survival of 12 months, and four died of acute nonlymphocytic leukemia (ANLL). Of 12 patients with complex defects, 11 had a complete or partial loss of a chromosome 5 and a complete or partial loss of the long arm of a chromosome 7 or 20. They had a poor median survival of four months, and six patients died of ANLL. Although the French-American-British (FAB) classification was also found to have some prognostic value, FAB subgroups were chromosomally heterogeneous and showed less dramatic differences in median survival than the larger chromosomal subgroups. We have shown, for the first time, that a refined chromosomal analysis is an independent prognostic indicator in de novo MDS and may be helpful in establishing therapeutic approaches in this difficult group of heterogeneous disorders.

scholarly journals Characterization of a Rare Mosaic Unbalanced Translocation of t(3;12) in a Patient With Neurodevelopmental Disorders

2021 ◽  
Author(s):  
Xiaolin Hu ◽  
Elizabeth K Baker ◽  
Jodie Johnson ◽  
Stephanie Balow ◽  
Loren D.M. Pena ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Chromosome Analysis ◽  
Chromosome 12 ◽  
Derivative Chromosome ◽  
Unbalanced Translocation ◽  
Balanced Translocation ◽  
Chromosomal Disorders ◽  
History Of

Abstract Background Unbalanced translocations may be de novo or inherited from one parent carrying the balanced form and are usually present in all cells. Mosaic unbalanced translocations are extremely rare with a highly variable phenotype depending on the tissue distribution and level of mosaicism. Mosaicism for structural chromosomal abnormalities is clinically challenging for diagnosis and counseling due to the limitation of technical platforms and complex mechanisms, respectively. Here we report a case with a tremendously rare maternally-derived mosaic unbalanced translocation of t(3;12), and we illustrate the unreported complicated mechanism using single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and chromosome analyses. Case Presentation: An 18-year-old female with a history of microcephaly, pervasive developmental disorder, intellectual disability, sensory integration disorder, gastroparesis, and hypotonia presented to our genetics clinic. She had negative karyotype by parental report but no other genetic testing performed previously. SNP microarray analysis revealed a complex genotype including 8.4 Mb terminal mosaic duplication on chromosome 3 (3p26.3->3p26.1) with the distal 5.7 Mb involving two parental haplotypes and the proximal 2.7 Mb involving three parental haplotypes, and a 6.1 Mb terminal mosaic deletion on chromosome 12 (12p13.33->12p13.31) with no evidence for a second haplotype. Adjacent to the mosaic deletion is an interstitial mosaic copy-neutral region of homozygosity (1.9 Mb, 12p13.31). The mother of this individual was confirmed by chromosome analysis and FISH that she carries a balanced translocation, t(3;12)(p26.1;p13.31). Conclusion Taken together, the proband, when at the stage of a zygote, likely carried the derivative chromosome 12 from this translocation, and a postzygotic mitotic recombination event occurred between the normal paternal chromosome 12 and maternal derivative chromosome 12 to “correct” the partial 3p trisomy and partial deletion of 12p. To the best of our knowledge, it is the first time that a mechanism utilizing a combined cytogenetic and cytogenomic approach, and we believe it expands our knowledge of mosaic structural chromosomal disorders and provides new insight into clinical management and genetic counseling.

scholarly journals Induction of Promoter DNA Methylation Upon High-Pressure Spraying of Double-Stranded RNA in Plants

Agronomy ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 789
Author(s):  
Athanasios Dalakouras ◽  
Ioannis Ganopoulos
Keyword(s):  
High Pressure ◽  
De Novo ◽  
Epigenetic Changes ◽  
Double Stranded Rna ◽  
Rna Molecules ◽  
Promoter Sequences ◽  
Promoter Dna Methylation ◽  
Promoter Dna ◽  
First Time ◽  
De Novo Methylation

Exogenous application of RNA molecules is a potent method to trigger RNA interference (RNAi) in plants in a transgene-free manner. So far, all exogenous RNAi (exo-RNAi) applications have aimed to trigger mRNA degradation of a given target. However, the issue of concomitant epigenetic changes was never addressed. Here, we report for the first time that high-pressure spraying of dsRNAs can trigger de novo methylation of promoter sequences in plants.

scholarly journals A Novel Intronic Pathogenic Variant in STAR With a Dominant Negative Mechanism Causes Attenuated Lipoid Congenital Adrenal Hyperplasia

2021 ◽  
Vol 9 ◽  
pp. 232470962110146
Author(s):  
Erin Finn ◽  
Kimberly Kripps ◽  
Christina Chambers ◽  
Michele Rapp ◽  
Naomi J. L. Meeks ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive ◽  
De Novo ◽  
Dominant Negative ◽  
Adrenal Hyperplasia ◽  
Primary Adrenal Insufficiency ◽  
Heterozygous Variant ◽  
Novel Variant ◽  
Autosomal Recessive Condition ◽  
Clinically Significant

Lipoid congenital adrenal hyperplasia (LCAH) is typically inherited as an autosomal recessive condition. There are 3 reports of individuals with a dominantly acting heterozygous variant leading to a clinically significant phenotype. We report a 46,XY child with a novel heterozygous intronic variant in STAR resulting in LCAH with an attenuated genital phenotype. The patient presented with neonatal hypoglycemia and had descended testes with a fused scrotum and small phallus. Evaluation revealed primary adrenal insufficiency with deficiencies of cortisol, aldosterone, and androgens. He was found to have a de novo heterozygous novel variant in STAR: c.65-2A>C. We report a case of a novel variant and review of other dominant mutations at the same position in the literature. Clinicians should be aware of the possibility of attenuated genital phenotypes of LCAH and the contribution of de novo variants in STAR at c.65-2 to the pathogenesis of that phenotype.

scholarly journals De Novo Partial 13q22-q34 Trisomy with Typical Neurological and Immunological Findings: A Case Report with New Genetic Insights

2020 ◽  
Vol 11 (1) ◽  
pp. 21
Author(s):  
Claudia Brogna ◽  
Valentina Milano ◽  
Barbara Brogna ◽  
Lara Cristiano ◽  
Giuseppe Rovere ◽  
...  
Keyword(s):  
Case Report ◽  
De Novo ◽  
Partial Trisomy ◽  
Cerebral Vasculitis ◽  
Radiological Findings ◽  
Cerebral Lesions ◽  
Brain Malformations ◽  
Vermian Hypoplasia ◽  
Callosal Dysgenesis ◽  
First Time

The partial trisomy 13q encompasses an extensive variability of phenotypic and radiological findings including leukoencephalopathy and brain malformations such as holoprosencephaly, callosal dysgenesis, hippocampal hypoplasia, olfactory hypoplasia, and vermian hypoplasia. We report for the first time a case of a 23-year-old patient affected by de novo partial 13q22.1q34 trisomy (41.7 Mb, 72,365,975-114,077,122x3) presenting with hemiparesis related to both ischemic and haemorrhagic cerebral lesions compatible with cerebral vasculitis due to a possible combination of genetic and immunological interaction.

scholarly journals Abrogation of RUNX1 gene expression in de novo myelodysplastic syndrome with t(4;21)(q21;q22)

Haematologica ◽  
2011 ◽  
Vol 97 (4) ◽  
pp. 534-537 ◽  
Author(s):  
A. Rio-Machin ◽  
J. Menezes ◽  
A. Maiques-Diaz ◽  
X. Agirre ◽  
B. I. Ferreira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myelodysplastic Syndrome ◽  
De Novo ◽  
Runx1 Gene

scholarly journals Jumping Translocations of 1q in Myelodysplastic Syndrome and Acute Myeloid Leukemia: Report of Three Cases and Review of Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
T. Couture ◽  
K. Amato ◽  
A. DiAdamo ◽  
P. Li
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Pericentromeric Region ◽  
Review Of Literature ◽  
Cell Lineages ◽  
Chromosome 1Q ◽  
Acrocentric Chromosomes ◽  
Acute Myeloid

Jumping translocations of 1q refer to the break-off of chromosome 1q as a donor fusing to two or more recipient chromosomes. We detected jumping translocations of 1q in three patients with initial diagnosis of myelodysplastic syndrome (MDS) and later progression to acute myeloid leukemia (AML). Review of literature found jumping translocations of 1q in 30 reported cases of MDS and AML. The cytogenetic findings from these 33 cases showed that seven cases had a stemline clone and 26 cases had de novo jumping translocations of 1q in which 5% of cell lineages had additional structural rearrangements. In 75% of cases, the 1q donor jumped to the short arm of recipient acrocentric chromosomes. Approximately 82% of the fusions occurred in the telomeric regions of short and long arms and 18% occurred in the pericentric or interstitial regions of recipient chromosomes. Hypomethylation of the donor 1q pericentromeric region and shortened telomeres in recipient chromosomes were associated with the formation of jumping translocations. Jumping translocations of 1q as an indication of chromosomal instability pose high risk for progression of MDS to AML and a poor prognosis. Further understanding of underlying genomic defects and their clinical significance will improve overall treatment and patient care.

scholarly journals Consistency and Stability of Motor Subtype Classifications in Patients With de novo Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Jingru Ren ◽  
Chenxi Pan ◽  
Yuqian Li ◽  
Lanting Li ◽  
Ping Hua ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Classification Systems ◽  
Motor Symptoms ◽  
Chi Squared ◽  
Baseline Evaluation ◽  
The Stability ◽  
First Time ◽  
Non Motor Symptoms

ObjectivePatients with Parkinson’s disease (PD) are commonly classified into subtypes based on motor symptoms. The aims of the present study were to determine the consistency between PD motor subtypes, to assess the stability of PD motor subtypes over time, and to explore the variables influencing PD motor subtype stability.MethodsThis study was part of a longitudinal study of de novo PD patients at a single center. Based on three different motor subtype classification systems proposed by Jankovic, Schiess, and Kang, patients were respectively categorized as tremor-dominant/indeterminate/postural instability and gait difficulty (TD/indeterminate/PIGD), TDS/mixedS/akinetic-rigidS (ARS), or TDK/mixedK/ARK at baseline evaluation and then re-assessed 1 month later. Demographic and clinical characteristics were recorded at each evaluation. The consistency between subtypes at baseline evaluation was assessed using Cohen’s kappa coefficient (κ). Additional variables were compared between PD subtype groups using the two-sample t-test, Mann–Whitney U-test or Chi-squared test.ResultsOf 283 newly diagnosed, untreated PD patients, 79 were followed up at 1 month. There was fair agreement between the Jankovic, Schiess, and Kang classification systems (κS = 0.383 ± 0.044, κK = 0.360 ± 0.042, κSK = 0.368 ± 0.038). Among the three classification systems, the Schiess classification was the most stable and the Jankovic classification was the most unstable. The non-motor symptoms questionnaire (NMSQuest) scores differed significantly between PD patients with stable and unstable subtypes based on the Jankovic classification (p = 0.008), and patients with a consistent subtype had more severe NMSQuest scores than patients with an inconsistent subtype.ConclusionFair consistency was observed between the Jankovic, Schiess, and Kang classification systems. For the first time, non-motor symptoms (NMSs) scores were found to influence the stability of the TD/indeterminate/PIGD classification. Our findings support combining NMSs with motor symptoms to increase the effectiveness of PD subtypes.

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