scholarly journals Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes

2013 ◽  
Vol 164 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Daria V. Babushok ◽  
Hongbo M. Xie ◽  
Jacquelyn J. Roth ◽  
Nieves Perdigones ◽  
Timothy S. Olson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Single Nucleotide Polymorphism ◽  
Single Nucleotide Polymorphism Array ◽  
Bone Marrow Failure ◽  
Nucleotide Polymorphism ◽  
Array Analysis ◽  
Single Nucleotide ◽  
Genetic Changes

Single Nucleotide Polymorphism Array Analysis Of Bone Marrow Failure Patients Reveals Characteristic Patterns Of Genetic Changes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3710-3710
Author(s):  
Daria V. Babushok ◽  
Hongbo M. Xie ◽  
Jacquelyn J. Roth ◽  
Nieves Perdigones ◽  
Timothy S. Olson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Single Nucleotide Polymorphism ◽  
Copy Number ◽  
Clinical Utility ◽  
Bone Marrow Failure ◽  
Clonal Evolution ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Genetic Changes ◽  
Conventional Cytogenetics

Abstract Bone marrow failure syndromes (BMFS) are a diverse group of rare life-threatening blood disorders characterized by inadequate hematopoiesis, clonal evolution, and increased risk of hematologic malignancies. Despite recent advances in the understanding of the molecular pathogenesis of BMFS, the ability to diagnose, risk-stratify, and treat patients with these rare disorders remains limited. In both the acquired and the inherited BMFS, the major contributors to mortality are complications of progressive cytopenias, and, albeit to a lesser extent—transformation to myelodysplastic syndrome (MDS) and acute myeloid leukemia. The main predictor of malignant transformation is acquisition of clonal cytogenetic abnormalities. Recently, single nucleotide polymorphism arrays (SNP-A) were proposed as a promising tool for high resolution cytogenetic analysis and surveillance of early clonal changes in BMFS, however, their clinical utility still remains to be established. In 2009, the Comprehensive Bone Marrow Failure Center at the Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania incorporated high-density SNP-A as an adjunct to conventional cytogenetics in evaluation of BMFS patients. Here we present a comprehensive analysis of genetic changes in BMFS using 124 SNP-A from 91 patients, who were referred for evaluation of bone marrow failure. SNP-A genotyping was correlated with medical histories, hematopathology, cytogenetic, and molecular data. To assess the potential role of SNP-A in screening for early clonal evolution, longitudinal analysis of SNP-A was performed in 25 patients. We found that acquired copy number-neutral loss of heterozygosity (CN-LOH) was significantly more frequent in acquired aplastic anemia (aAA) than in other BMFS (OR 12.240, 95% CI 1.333-573.696, p<0.01). In contrast, acquired copy number alterations (CNAs) were more typical of MDS and unclassified BMFS. Extended tracts of homozygosity were common, frequently unmasking recessive loci in cases of inherited BMFS. Copy number variants (CNVs) were frequently polymorphic, and we identified several CNVs that are enriched in patients with aAA and neutropenia and may serve as disease modifiers. Clinical utilization analysis revealed that SNP-A can be helpful as an adjunct to conventional cytogenetics at the time of initial diagnosis (e.g. to identify regions of acquired CN-LOH and inherited homozygosity, acquired CNAs with a small clone size, and CNVs). Our longitudinal analysis showed that the likelihood of detecting a new acquired abnormality in a follow-up SNP-A was significantly higher in the setting of relapse than in the setting of stable disease (OR 27, 95% CI 1.23 to 808.54, p=0.035). Our results suggest that acquired CN-LOH is a general phenomenon in aAA, likely mechanistically and prognostically distinct from typical CN-LOH of myeloid malignancies. Our analysis of clinical utility of SNP-A shows the highest yield of detecting new clonal hematopoiesis at diagnosis and at relapse. Disclosures: No relevant conflicts of interest to declare.

Single nucleotide polymorphism array analysis in men with idiopathic azoospermia or oligoasthenozoospermia syndrome

2013 ◽  
Vol 100 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Anne Frühmesser ◽  
Peter H. Vogt ◽  
Jutta Zimmer ◽  
Martina Witsch-Baumgartner ◽  
Christine Fauth ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Single Nucleotide Polymorphism Array ◽  
Nucleotide Polymorphism ◽  
Array Analysis ◽  
Single Nucleotide

Single nucleotide polymorphism array analysis to predict clinical outcome in neuroblastoma patients

2006 ◽  
Vol 41 (12) ◽  
pp. 2032-2036 ◽  
Author(s):  
Eiso Hiyama ◽  
Hiroaki Yamaoka ◽  
Arata Kamimatsuse ◽  
Yoshiyuki Onitake ◽  
Keiko Hiyama ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Clinical Outcome ◽  
Single Nucleotide Polymorphism Array ◽  
Nucleotide Polymorphism ◽  
Array Analysis ◽  
Single Nucleotide

scholarly journals Prenatal Diagnosis of 17p11.2 Copy Number Abnormalities Associated With Smith–Magenis and Potocki–Lupski Syndromes in Fetuses

2021 ◽  
Vol 12 ◽  
Author(s):  
Meiying Cai ◽  
Xianguo Fu ◽  
Liangpu Xu ◽  
Na Lin ◽  
Hailong Huang
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Prenatal Diagnosis ◽  
Copy Number ◽  
De Novo ◽  
Single Nucleotide Polymorphism Array ◽  
Copy Number Variant ◽  
Prenatal Ultrasound ◽  
Nucleotide Polymorphism ◽  
Array Analysis ◽  
Single Nucleotide

Smith-Magenis syndrome and Potocki-Lupski syndrome are rare autosomal dominant diseases. Although clinical phenotypes of adults and children have been reported, fetal ultrasonic phenotypes are rarely reported. A retrospective analysis of 6,200 pregnant women who received invasive prenatal diagnosis at Fujian Provincial Maternal and Child Health Hospital between October 2016 and January 2021 was performed. Amniotic fluid or umbilical cord blood was extracted for karyotyping and single nucleotide polymorphism array analysis. Single nucleotide polymorphism array analysis revealed six fetuses with copy number variant changes in the 17p11.2 region. Among them, one had a copy number variant microdeletion in the 17p11.2 region, which was pathogenically analyzed and diagnosed as Smith-Magenis syndrome. Five fetuses had copy number variant microduplications in the 17p11.2 region, which were pathogenically analyzed and diagnosed as Potocki-Lupski syndrome. The prenatal ultrasound phenotypes of the six fetuses were varied. The parents of two fetuses with Potocki-Lupski syndrome refused verification. Smith-Magenis syndrome in one fetus and Potocki-Lupski in another were confirmed as de novo. Potocki-Lupski syndrome in two fetuses was confirmed to be from maternal inheritance. The prenatal ultrasound phenotypes of Smith-Magenis syndrome and Potocki-Lupski syndrome in fetuses vary; single nucleotide polymorphism array analysis is a powerful diagnostic tool for these diseases. The ultrasonic phenotypes of these cases may enrich the clinical database.

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