scholarly journals Genomic and clinical findings in myeloid neoplasms with PDGFRB rearrangement

2021 ◽  
Author(s):  
Danika Di Giacomo ◽  
Martina Quintini ◽  
Valentina Pierini ◽  
Fabrizia Pellanera ◽  
Roberta La Starza ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism Array ◽  
Growth Factor Receptor ◽  
High Sensitivity ◽  
Clinical Findings ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Myeloid Neoplasm ◽  
Myeloid Neoplasms ◽  
Generation Sequencing ◽  
Low Dosage

AbstractPlatelet-derived growth factor receptor B (PDGFRB) gene rearrangements define a unique subgroup of myeloid and lymphoid neoplasms frequently associated with eosinophilia and characterized by high sensitivity to tyrosine kinase inhibition. To date, various PDGFRB/5q32 rearrangements, involving at least 40 fusion partners, have been reported. However, information on genomic and clinical features accompanying rearrangements of PDGFRB is still scarce. Here, we characterized a series of 14 cases with a myeloid neoplasm using cytogenetic, single nucleotide polymorphism array, and next-generation sequencing. We identified nine PDGFRB translocation partners, including the KAZN gene at 1p36.21 as a novel partner in a previously undescribed t(1;5)(p36;q33) chromosome change. In all cases, the PDGFRB recombination was the sole cytogenetic abnormality underlying the phenotype. Acquired somatic variants were mainly found in clinically aggressive diseases and involved epigenetic genes (TET2, DNMT3A, ASXL1), transcription factors (RUNX1 and CEBPA), and signaling modulators (HRAS). By using both cytogenetic and nested PCR monitoring to evaluate response to imatinib, we found that, in non-AML cases, a low dosage (100–200 mg) is sufficient to induce and maintain longstanding hematological, cytogenetic, and molecular remissions.

scholarly journals Compound heterozygous variants including a novel copy number variation in a child with atypical ataxia-telangiectasia: a case report

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hoo Young Lee ◽  
Dae-Hyun Jang ◽  
Jae-Won Kim ◽  
Dong-Woo Lee ◽  
Ja-Hyun Jang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Ataxia Telangiectasia ◽  
Single Nucleotide Polymorphism Array ◽  
Compound Heterozygous ◽  
Next Generation ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Pathogenic Variants ◽  
Number Variation ◽  
Generation Sequencing

Abstract Background Ataxia-telangiectasia is a rare autosomal recessive, neurodegenerative disorder caused by alterations in the ATM gene. The majority of ATM pathogenic variants are frameshift or nonsense variants which are predicted to truncate the whole ATM protein. Herein, we report on an ataxia telangiectasia child with atypical phenotype who was identified as compound heterozygous for two ATM variants involving a previously described pathogenic single nucleotide variation (SNV) and a novel copy number variation (CNV). Case presentation A 6-year-old boy presented with delayed development and oculomotor apraxia. Brain magnetic resonance imaging showed interval development of mild atrophy in the cerebellum. Serum alpha fetoprotein level was in normal range. Next-generation sequencing and single-nucleotide polymorphism array tests were performed. Next-generation sequencing revealed a heterozygous nonsense pathogenic variant in ATM, c.742C > T (p.Arg248Ter) inherited from the father. Single-nucleotide polymorphism array revealed a compound heterozygous CNV, arr[GRCh37] 11q22.3(10851766–108183226) × 1, 31460 bp (exons 24–40 deletion of ATM) inherited from the mother, which was validated by reverse transcription-polymerase chain reaction analysis (RT-PCR). We demonstrated that this variant (NM_000051.4:c.3403_6006del) generated a product of in-frame deletion of exon 24–40 of ATM (p.Ser1135_Gln2002del). Conclusions The compound heterozygosity for ATM variants involving a previously described pathogenic SNV and a novel CNV may be associated with the atypical clinical manifestations. This clinical report extends the genetic and phenotypic spectrum of ATM pathogenic variants in atypical ataxia-telangiectasia, thus making implementation of advanced analysis beyond the routine next-generation sequencing an important consideration in diagnosis and rehabilitation services for children with ataxia-telangiectasia.

scholarly journals High concordance between next generation sequencing and single-nucleotide polymorphism array in preimplantation genetic testing for aneuploid

2020 ◽  
Author(s):  
Zhanhui Ou ◽  
Zhiheng Chen ◽  
Yu Deng ◽  
Minna Yin ◽  
Ling Sun
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Next Generation Sequencing ◽  
Single Nucleotide Polymorphism Array ◽  
Snp Array ◽  
Concordance Rate ◽  
Next Generation ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
High Concordance ◽  
Generation Sequencing

Abstract Background: Single-nucleotide polymorphism array (SNP array) and next generation sequencing (NGS) in detecting chromosome aneuploidy are widely used in clinical work. Aims: To compare the concordance between NGS and SNP array in 67 embryos (from 23 couples). Methods: In the first part of the study, 28 blastocysts with unknown ploidy were both analyzed with NGS and SNP array. While in the second part, 39 with normal ploidy detected by NGS were re-analyzed with SNP array. Results: In the first part of the study, the concordance rate between NGS and SNP array was 92.9% (26/28). Among the 28 blastocysts, 18 were abnormal and 10 blastocysts were with normal ploidy status when analyzed by NGS. Among the 18 abnormal blastocysts, two blastocysts were with low level of mosaicism as analyzed by NGS, but euploid with SNP array. In the second part, concordance rate between NGS and SNP array was 100% (39/39). At last, one couple had no blastocyst to transfer. The other 22 couples were transferred with single blastocyst. Among them, two couples suffered abortions before 12 weeks, and the karyotype of villus was normal. One couple with only 1 normal blastocyst failed to conceive after the transfer. In total nineteen couples had healthy babies born. Conclusions: There was a high concordance rate between NGS and SNP array. But NGS was also able to detect mosaicism sensitively. Hence, using NGS for PGT-A may increase the chances of having a healthy and live newborn child.

scholarly journals A case of hypereosinophilic syndrome with STAT5b N642H mutation

2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
Feihong Ding ◽  
Chaoping Wu ◽  
Yun Li ◽  
Sudipto Mukherjee ◽  
Subha Ghosh ◽  
...  
Keyword(s):  
Complete Blood Count ◽  
Hypereosinophilic Syndrome ◽  
Organ Damage ◽  
Myeloid Neoplasm ◽  
Acute Eosinophilic Pneumonia ◽  
Myeloid Neoplasms ◽  
Somatic Signal ◽  
Generation Sequencing

ABSTRACT Hypereosinophilia is defined as persistent eosinophilia (>1.5 × 109/L). Hypereosinophilic syndrome (HES) is a term used to describe a group of disorders characterized by sustained hypereosinophilia associated with end-organ damage. Based on underlying molecular mechanism of eosinophilia, there are different subtypes of HES. Diagnosis of HES subtype can be challenging, especially in the absence of overt lymphoid/myeloid neoplasms or discernable secondary causes. Long-term outpatient follow-up with periodic complete blood count and repeated bone marrow biopsy may be needed to monitor disease activity. Somatic signal transducer and activation transcription 5b (STAT5b) N642H mutation was recently found to be associated with myeloid neoplasms with eosinophilia. We report a case of HES who presented with pulmonary embolism and acute eosinophilic pneumonia, found to have recurrent STAT5b N642H mutation by next-generation sequencing, suggesting possible underlying myeloid neoplasm.

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