scholarly journals Clinical Utility of the Addition of Molecular Genetic Testing to Newborn Screening for Sickle Cell Anemia

2021 ◽  
Vol 8 ◽  
Author(s):  
Lisa M. Shook ◽  
Deidra Haygood ◽  
Charles T. Quinn
Keyword(s):  
Genetic Testing ◽  
Newborn Screening ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Correct Diagnosis ◽  
Molecular Genetic ◽  
Final Diagnosis ◽  
The United States ◽  
Molecular Genetic Testing ◽  
Benign Condition

Sickle cell disease (SCD) is a group of related yet genetically complex hemoglobinopathies. Universal newborn screening (NBS) for SCD is performed in the United States and many other nations. Classical, protein-based laboratory methods are often adequate for the diagnosis of SCD but have specific limitations in the context of NBS. A particular challenge is the differentiation of sickle cell anemia (SCA) from the benign condition, compound heterozygosity for HbS and gene-deletion hereditary persistence of fetal hemoglobin (HbS/HPFH). We describe a sequential cohort of 44 newborns identified over 4.5 years who had molecular genetic testing incorporated into NBS for presumed SCA (an “FS” pattern). The final diagnosis was something other than SCA in six newborns (12%). Three (7%) had HbS/HPFH. All had a final, correct diagnosis at the time of their first scheduled clinic visit in our center (median 8 weeks of age). None received initial counseling for an incorrect diagnosis. In summary, genetic testing as a component of NBS for SCD is necessary to provide correct genetic counseling and education for all newborns' families at their first visit to a sickle cell center. Genetic testing also permits the use of early, pre-symptomatic hydroxyurea therapy by preventing infants with HbS/HPFH from receiving unnecessary therapy. We argue that genetic testing should be incorporated into contemporary NBS for SCD.

scholarly journals Multimorbidity in Pediatric Dermatology: Clinical Case

2020 ◽  
Vol 19 (6) ◽  
pp. 483-489
Author(s):  
Nikolay N. Murashkin ◽  
Alexander I. Materikin ◽  
Eduard T. Ambarchian ◽  
Roman V. Epishev ◽  
Leonid A. Opryatin ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Autosomal Recessive ◽  
Clinical Case ◽  
Correct Diagnosis ◽  
Molecular Genetic ◽  
Final Diagnosis ◽  
Molecular Genetic Testing ◽  
Pediatric Dermatology ◽  
Dominant Type ◽  
Recessive Type

Background. Nowadays, dermatoses with mixed clinical picture and resistant to classical management become more common. The presence of various genetic disorders typical for most chronic dermatoses may indicate possible combination of several nosologies.Clinical Case Description. The article presents the clinical case of multimorbid condition in 10 years old patient who has nucleotide variants in CARD14 and EXPH5 genes. Mutations in CARD14 gene are typical for patients with type 2 psoriasis and pityriasis rubra pilaris (autosomal dominant type), while mutations in EXPH5 gene are typical for patients with non-specific epidermolysis bullosa (autosomal recessive type). Mutation in the TGM1 gene that is described in patients with congenital ichthyosis (autosomal recessive type), pathogenic mutations in KRT74 gene typical for ectodermal dysplasia, hypotrichosis and uncombable hair syndrome, and mutations in the KRT86 gene typical for monilethrix were also revealed. Medical history taking and histological examination as well as clinical data evaluating are crucial for correct diagnosis. They allow to understand the absence of the such manifestations in relatives and reveal various pathological processes in the epidermis. Molecular genetic testing with new generation sequencing (NGS) helps to finally establish the diagnosis and determine the further tactics for patient management.Conclusion. Multidisciplinary approach and use of high-technology methods of examination and treatment (such as molecular genetic testing and biological therapy) are required for final diagnosis in severe forms of chronic dermatosis resistant to treatment and for decision on correct tactics for the further management of such patients.

Molecular Genetic Testing in the United States: Comparison with International Practice

2008 ◽  
Vol 12 (2) ◽  
pp. 187-193 ◽  
Author(s):  
Margaret M. McGovern ◽  
Rob Elles ◽  
Elettra Ronchi ◽  
Joe Boone ◽  
Ira M. Lubin
Keyword(s):  
United States ◽  
Genetic Testing ◽  
Molecular Genetic ◽  
The United States ◽  
Molecular Genetic Testing

Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by molecular genetic testing

2005 ◽  
Vol 152 (6) ◽  
pp. 1353-1356 ◽  
Author(s):  
M. Akiyama ◽  
Y. Tsuji-Abe ◽  
M. Yanagihara ◽  
K. Nakajima ◽  
H. Kodama ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Correct Diagnosis ◽  
Molecular Genetic ◽  
Molecular Genetic Testing

scholarly journals Second Tier Molecular Genetic Testing in Newborn Screening for Pompe Disease: Landscape and Challenges

2020 ◽  
Vol 6 (2) ◽  
pp. 32 ◽  
Author(s):  
Laurie D. Smith ◽  
Matthew N. Bainbridge ◽  
Richard B. Parad ◽  
Arindam Bhattacharjee
Keyword(s):  
Genetic Testing ◽  
Newborn Screening ◽  
Pompe Disease ◽  
False Positive ◽  
Clinical Decision Making ◽  
Molecular Genetic ◽  
Screening Tests ◽  
Molecular Genetic Testing ◽  
Second Tier ◽  
Positive Results

Pompe disease (PD) is screened by a two tier newborn screening (NBS) algorithm, the first tier of which is an enzymatic assay performed on newborn dried blood spots (DBS). As first tier enzymatic screening tests have false positive results, an immediate second tier test on the same sample is critical in resolving newborn health status. Two methodologies have been proposed for second tier testing: (a) measurement of enzymatic activities such as of Creatine/Creatinine over alpha-glucosidase ratio, and (b) DNA sequencing (a molecular genetics approach), such as targeted next generation sequencing. (tNGS). In this review, we discuss the tNGS approach, as well as the challenges in providing second tier screening and follow-up care. While tNGS can predict genotype-phenotype effects when known, these advantages may be diminished when the variants are novel, of unknown significance or not discoverable by current test methodologies. Due to the fact that criticisms of screening algorithms that utilize tNGS are based on perceived complexities, including variant detection and interpretation, we clarify the actual limitations and present the rationale that supports optimizing a molecular genetic testing approach with tNGS. Second tier tNGS can benefit clinical decision-making through the use of the initial NBS DBS punch and rapid turn-around time methodology for tNGS, that includes copy number variant analysis, variant effect prediction, and variant ‘cut-off’ tools for the reduction of false positive results. The availability of DNA sequence data will contribute to the improved understanding of genotype-phenotype associations and application of treatment. The ultimate goal of second tier testing should enable the earliest possible diagnosis for the earliest initiation of the most effective clinical interventions in infants with PD.

scholarly journals Diagnosing Paraproteinemic Keratopathy: A Case Report

2021 ◽  
pp. 337-343
Author(s):  
Eugenie Mok ◽  
Ka Wai Kam ◽  
Anthony J. Aldave ◽  
Alvin L. Young
Keyword(s):  
Optical Coherence Tomography ◽  
Genetic Testing ◽  
Serum Protein ◽  
Molecular Genetic ◽  
Anterior Segment ◽  
Protein Electrophoresis ◽  
Serum Protein Electrophoresis ◽  
Optical Coherence ◽  
Molecular Genetic Testing ◽  
Corneal Opacities

A 65-year-old man presented with bilateral, painless, progressive blurring of vision over 9 years. Slit-lamp examination revealed bilateral subepithelial corneal opacities in clusters located at the mid-periphery. Anterior segment optical coherence tomography, in vivo confocal microscopy (IVCM), serum protein electrophoresis, and molecular genetic testing were performed to evaluate the cause of corneal opacities. Anterior segment optical coherence tomography revealed a band-like, hyperreflective lesion in the Bowman layer and anterior stroma of both corneas. IVCM revealed hyperreflective deposits in the epithelium, anterior stroma, and endothelium. Serum protein electrophoresis identified the presence of paraproteins (immunoglobulin kappa), and molecular genetic testing revealed absence of mutations in the transforming growth factor beta-induced gene (<i>TGFBI</i>) and collagen type XVII alpha 1 gene (<i>COL17A1</i>). The ocular diagnosis of paraproteinemic keratopathy eventually led to a systemic diagnosis of monoclonal gammopathy of undetermined significance by our hematologist/oncologist. Paraproteinemic keratopathy is a rare differential diagnosis in patients with bilateral corneal opacities and therefore may be misdiagnosed as corneal dystrophy or neglected as scars. In patients with bilateral corneal opacities of unknown cause, serological examination, adjunct anterior segment imaging, and molecular genetic testing play a role in establishing the diagnosis.

scholarly journals Initial Diagnostic Workup of Acute Leukemia: Guideline From the College of American Pathologists and the American Society of Hematology

2017 ◽  
Vol 141 (10) ◽  
pp. 1342-1393 ◽  
Author(s):  
Daniel A. Arber ◽  
Michael J. Borowitz ◽  
Melissa Cessna ◽  
Joan Etzell ◽  
Kathryn Foucar ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Clinical Information ◽  
Molecular Genetic Testing ◽  
Acute Leukemias ◽  
Prognostic Evaluation ◽  
The Public ◽  
American Society

Context.— A complete diagnosis of acute leukemia requires knowledge of clinical information combined with morphologic evaluation, immunophenotyping and karyotype analysis, and often, molecular genetic testing. Although many aspects of the workup for acute leukemia are well accepted, few guidelines have addressed the different aspects of the diagnostic evaluation of samples from patients suspected to have acute leukemia. Objective.— To develop a guideline for treating physicians and pathologists involved in the diagnostic and prognostic evaluation of new acute leukemia samples, including acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage. Design.— The College of American Pathologists and the American Society of Hematology convened a panel of experts in hematology and hematopathology to develop recommendations. A systematic evidence review was conducted to address 6 key questions. Recommendations were derived from strength of evidence, feedback received during the public comment period, and expert panel consensus. Results.— Twenty-seven guideline statements were established, which ranged from recommendations on what clinical and laboratory information should be available as part of the diagnostic and prognostic evaluation of acute leukemia samples to what types of testing should be performed routinely, with recommendations on where such testing should be performed and how the results should be reported. Conclusions.— The guideline provides a framework for the multiple steps, including laboratory testing, in the evaluation of acute leukemia samples. Some aspects of the guideline, especially molecular genetic testing in acute leukemia, are rapidly changing with new supportive literature, which will require on-going updates for the guideline to remain relevant.

Bioelectronic Sensor Technology for Detection of Cystic Fibrosis and Hereditary Hemochromatosis Mutations

2003 ◽  
Vol 127 (12) ◽  
pp. 1565-1572
Author(s):  
Susan H. Bernacki ◽  
Daniel H. Farkas ◽  
Wenmei Shi ◽  
Vivian Chan ◽  
Yenbou Liu ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Testing ◽  
Cell Lines ◽  
Molecular Genetic ◽  
Hereditary Hemochromatosis ◽  
The Other ◽  
Molecular Diagnostic ◽  
Molecular Genetic Testing ◽  
Diagnostic Applications ◽  
Lymphocyte Cell

Abstract Context.—Bioelectronic sensors, which combine microchip and biological components, are an emerging technology in clinical diagnostic testing. An electronic detection platform using DNA biochip technology (eSensor) is under development for molecular diagnostic applications. Owing to the novelty of these devices, demonstrations of their successful use in practical diagnostic applications are limited. Objective.—To assess the performance of the eSensor bioelectronic method in the validation of 6 Epstein-Barr virus–transformed blood lymphocyte cell lines with clinically important mutations for use as sources of genetic material for positive controls in clinical molecular genetic testing. Two cell lines carry mutations in the CFTR gene (cystic fibrosis), and 4 carry mutations in the HFE gene (hereditary hemochromatosis). Design.—Samples from each cell line were sent for genotype determination to 6 different molecular genetic testing facilities, including the laboratory developing the DNA biochips. In addition to the bioelectronic method, at least 3 different molecular diagnostic methods were used in the analysis of each cell line. Detailed data were collected from the DNA biochip output, and the genetic results were compared with those obtained using the more established methods. Results.—We report the successful use of 2 applications of the bioelectronic platform, one for detection of CFTR mutations and the other for detection of HFE mutations. In all cases, the results obtained with the DNA biochip were in concordance with those reported for the other methods. Electronic signal output from the DNA biochips clearly differentiated between mutated and wild-type alleles. This is the first report of the use of the cystic fibrosis detection platform. Conclusions.—Bioelectronic sensors for the detection of disease-causing mutations performed well when used in a “real-life” situation, in this case, a validation study of positive control blood lymphocyte cell lines with mutations of public health importance. This study illustrates the practical potential of emerging bioelectronic DNA detection technologies for use in current molecular diagnostic applications.

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