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PubMed | Genzyme and Esoterix Genetic Laboratories LLC
Type: Journal Article | Journal: Molecular genetics and metabolism | Year: 2014

Pompe disease is caused by a deficiency of acid -glucosidase (GAA; EC, 3.2.1.20), and the infantile-onset form is rapidly fatal if left untreated. However, recombinant human GAA (rhGAA) enzyme replacement therapy (ERT) extends survival for infantile Pompe patients. Although cross-reactive immunologic material (CRIM)-negative patients, who lack detectable endogenous GAA, mount an immune response to rhGAA that renders the therapy ineffective, timely induction of immune tolerance in these patients may improve clinical outcomes. Previously, CRIM status has been determined by Western blot analysis in cultured skin fibroblasts, a process that can take a few weeks. We present a blood-based CRIM assay that can yield results within 48 to 72 h. Results from this assay have been confirmed by GAA Western blot analysis in fibroblasts or by GAA sequencing in a small number of Pompe disease patients. Rapid classification of CRIM status will assist in identifying the most effective treatment course and minimizing treatment delays in patients with infantile-onset Pompe disease.


Trademark
Esoterix Genetic Laboratories Llc and Genzyme | Date: 2010-09-07

Computer software for controlling and managing patient medical information; Computer software for creating searchable databases of patient medical information and data.


Massingham L.J.,Floating Hospital for Children at Tufts Medical Center | Johnson K.L.,Tufts University | Scholl T.M.,Esoterix Genetic Laboratories LLC | Slonim D.K.,Tufts University | And 2 more authors.
Human Genetics | Year: 2014

Turner syndrome is a sex chromosome aneuploidy with characteristic malformations. Amniotic fluid, a complex biological material, could contribute to the understanding of Turner syndrome pathogenesis. In this pilot study, global gene expression analysis of cell-free RNA in amniotic fluid supernatant was utilized to identify specific genes/organ systems that may play a role in Turner syndrome pathophysiology. Cell-free RNA from amniotic fluid of five mid-trimester Turner syndrome fetuses and five euploid female fetuses matched for gestational age was extracted, amplified, and hybridized onto Affymetrix® U133 Plus 2.0 arrays. Significantly differentially regulated genes were identified using paired t tests. Biological interpretation was performed using Ingenuity Pathway Analysis and BioGPS gene expression atlas. There were 470 statistically significantly differentially expressed genes identified. They were widely distributed across the genome. XIST was significantly down-regulated (p < 0.0001); SHOX was not differentially expressed. One of the most highly represented organ systems was the hematologic/immune system, distinguishing the Turner syndrome transcriptome from other aneuploidies we previously studied. Manual curation of the differentially expressed gene list identified genes of possible pathologic significance, including NFATC3, IGFBP5, and LDLR. Transcriptomic differences in the amniotic fluid of Turner syndrome fetuses are due to genome-wide dysregulation. The hematologic/immune system differences may play a role in early-onset autoimmune dysfunction. Other genes identified with possible pathologic significance are associated with cardiac and skeletal systems, which are known to be affected in females with Turner syndrome. The discovery-driven approach described here may be useful in elucidating novel mechanisms of disease in Turner syndrome. © 2014, Springer-Verlag Berlin Heidelberg.


Karimov C.B.,Massachusetts General Hospital | Moragianni V.A.,Beth Israel Deaconess Medical Center | Cronister A.,Esoterix Genetic Laboratories LLC | Srouji S.,Brigham and Women's Hospital | And 5 more authors.
Human Reproduction | Year: 2011

Background: The FMR1 premutation is associated with overt primary ovarian insufficiency (POI). However, its prevalence in women with occult POI (i.e. menstrual cycles, but impaired ovarian response) has not been examined. We hypothesized that both the FMR1 premutation and intermediate allele is more frequent in infertile women with occult POI than in controls, and that a repeat length cutoff might predict occult POI. Methods: All subjects were menstruating women <42 years old and with no family history of unexplained mental retardation, autism or fragile X syndrome. Cases had occult POI defined by elevated FSH or poor response to gonadotrophin therapy (n 535). Control subjects (n=521) had infertility from other causes or were oocyte donors. Prevalence of the FMR1 premutation and intermediate alleles was examined and allele length was compared between controls and women with occult POI. Results: The frequency of the premutation (7/535 versus 1/521; P< 0.05) and intermediate alleles (17/535 versus 7/521; P< 0.05) was higher in women with occult POI than in controls. The allele with the greatest number of CGG repeats was longer in women with occult POI compared with controls (32.7 ± 7.1 versus 31.6 ± 4.3; P< 0.01). A receiver operating characteristic curve examining repeat length as a test for occult POI had an area of 0.56 ± 0.02 (P< 0.01). A repeat cutoff of 45 had a specificity of 98, but a sensitivity of only 5 to identify occult POI. The positive predictive value was only 21 for a fertility population that has ∼22 of its patients with occult POI. Conclusions: The data suggest that FMR1 premutations and intermediate alleles are increased in women with occult POI. Thus, FMR1 testing should be performed in these women as some will have fragileX-associated POI. Although the FMR1 repeat lengths were longer in women with occult POI, the data do not support the use of a repeat length cutoff to predict occult POI. © 2011 The Author Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Leo A.,Esoterix Genetic Laboratories LLC | Walker A.M.,Esoterix Genetic Laboratories LLC | Lebo M.S.,Esoterix Genetic Laboratories LLC | Lebo M.S.,Harvard University | And 3 more authors.
Journal of Molecular Diagnostics | Year: 2012

Array-based comparative genome hybridization (aCGH) is a powerful, data-intensive technique used to identify genomic copy number variation throughout the human genome. The use of aCGH clinically to identify pathogenic copy number aberrations is becoming common, and the statistical and mathematical algorithms used in aCGH data analysis play an important role in determining the performance of these platforms. Interpretation of aCGH data can be complicated by a platform-independent technical artifact described as GC-waves, which are wave patterns in CGH data correlating to regional GC-content of the human genome that can reduce the clinical specificity and sensitivity of aCGH platforms. We describe an automated GC-wave correction algorithm and techniques to understand how the correction affects the analytical performance of aCGH. This GC-correction algorithm was effective at mitigating GC-wave effects. After correction, array data were measurably improved by the algorithm, demonstrating improvements in specificity and sensitivity and in overall data quality. © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology.


Dong H.,Esoterix Genetic Laboratories LLC | Yang H.-S.,Esoterix Genetic Laboratories LLC | Jagannath S.,Mount Sinai School of Medicine | Stephenson C.F.,Esoterix Genetic Laboratories LLC | And 3 more authors.
Clinical Lymphoma, Myeloma and Leukemia | Year: 2012

Background: Routine cytogenetic analysis of plasma cell neoplasms (PCNs) has a low sensitivity. Conventional fluorescence in situ hybridization (FISH) is not plasma cell (PC) specific and results are diluted by other cells in the sample. Although PC-specific FISH testing has been recommended for multiple myeloma (MM) risk stratification, eg, by combining cytoplasmic immunoglobulin (cIg) staining with FISH, the benefits of cIg FISH have never been directly demonstrated in a controlled study. Patients and Methods: Seventy-five samples from patients with PCNs were analyzed by concomitant conventional FISH and cIg FISH with probes for t(4;14), t(11;14), t(14;16), -13, 17p-, and +3. The results were compared for their reliability, specificity, and consistency. Results: Apart from marginally improving detection threshold in samples with low PC burden, cIg FISH identified more abnormal cases (50 vs. 47 cases) and more chromosome abnormalities (113 vs. 103 events) than did conventional FISH. It differentiated del(13q) in myelodysplasia from MM. Remarkably, cIg FISH consistently identified a high percentage of abnormal PCs in all cases. It detected IGH translocation in 78% to 100% of PCs in all but 2 positive cases, whereas conventional FISH detected 0% to 46% in these cases (median, 91% vs. 9%). The abnormal cells found in patients with 17p- were 19% to 96% by cIg FISH vs. 0% to 13% by conventional FISH (median, 54% vs. 9%). Cases with insufficient PCs for cIg FISH had only normal conventional FISH results. Conclusion: CIg FISH improves reliability of FISH testing for PCNs by eliminating borderline results. In myelomas with an IGH translocation, myeloma cells invariably carry the abnormality. © 2012 Elsevier Inc.


Embodiments of the present invention provide methods for the enrichment of rare microparticles, cells, or nucleic acids from a complex mixture using serial size exclusion filtration. Also provided are less invasive methods for detecting chromosomal or genetic abnormalities in a fetus, by enriching fetal microparticles in maternal plasma using serial size exclusion filtration, and isolating and analyzing the fetal nucleic acids from the fetal microparticles. Methods for diagnosis of diseases such as cancer are also provided, including enriching disease specific microparticles in the patients plasma using serial size exclusion filtration, and isolating and analyzing the nucleic acids from the disease specific microparticles.


Patent
Esoterix Genetic Laboratories LLC | Date: 2016-05-04

Systems and methods for analyzing copy number of a target locus, detecting a disease associated with abnormal copy number of a target gene or a carrier thereof.


Patent
Esoterix Genetic Laboratories LLC | Date: 2015-07-28

The invention provides methods for detecting and monitoring diseases associated with genetic abnormalities in a subject.


Patent
Esoterix Genetic Laboratories LLC | Date: 2012-01-31

Methods for enriching specific microparticles, such as fetal microparticles or disease specific microparticles, in a biological sample are disclosed. In certain embodiments, the methods include combining a biological sample with a molecule that binds specific microparticles, and separating fractions of the biological sample, wherein the fraction that contains the binding molecule is enriched for the specific microparticles. Also disclosed are methods for enriching fetal nucleic acids by enriching fetal microparticles in a fraction of the biological sample and isolating nucleic acids from the enriched fraction. Methods for facilitating prenatal diagnosis of fetal chromosomal abnormalities are disclosed. In certain embodiments, the methods include combining a biological sample with a molecule that binds fetal microparticles, separating fractions of the biological sample, isolating nucleic acids from the fraction enriched for fetal microparticles, and analyzing the nucleic acids for the presence of a mutation.

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