Addendum: Technical standards and guidelines: Molecular genetic testing for ultra-rare disorders

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.

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

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2016-0504-cp ◽

2017 ◽

Vol 141 (10) ◽

pp. 1342-1393 ◽

Cited By ~ 50

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.

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Molecular genetic testing to diagnose malignant hyperthermia susceptibility

Journal of Clinical Anesthesia ◽

10.1016/j.jclinane.2007.12.011 ◽

2008 ◽

Vol 20 (3) ◽

pp. 161-163 ◽

Cited By ~ 3

Author(s):

Thierry Girard ◽

Ronald S. Litman

Keyword(s):

Genetic Testing ◽

Malignant Hyperthermia ◽

Molecular Genetic ◽

Malignant Hyperthermia Susceptibility ◽

Molecular Genetic Testing

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

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-1565-bstfdo ◽

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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STUDY OF CLINICAL CASES OF MYOCHE’S MYOPATHY AND DIFFERENTIAL DIAGNOSIS WITH OTHER TYPES OF ADVERSE MYOPATHIES

Odes’kij medičnij žurnal (The Odessa Medical Journal) ◽

10.54229/2226-2008-2021-5-14 ◽

2021 ◽

Author(s):

K. Sarazhyna ◽

Y. Solodovnikova ◽

A. Son

Keyword(s):

Case Report ◽

Genetic Testing ◽

Skeletal Muscles ◽

Molecular Genetic ◽

Clinical Signs ◽

Lower Limbs ◽

Molecular Genetic Testing ◽

Membrane Repair ◽

Rare Type ◽

A Cell

Markesbery-Griggs myopathy, Miyoshi type (MM) is a rare type of myopathy, a form muscular dystrophy with the main involvement of the lower girdle and distal parts of the legs. Due to complexity of genetic testing, the diagnosis is mainly made on the neurological examination of the patient, which adds value to this case report. The childhood or adolescence onset of the disease is characterized initially by the calf muscles` wasting, accompanied by the severe elevation of the serum creatine kinase, as well as a slowly progressive ascending course. The disease refers to dysferlinopathies with various mutations in the DYSF gene. The dysferlin protein is localized in the plasma membrane and in the T-tubule system of skeletal muscles. Physiologically, skeletal muscles are constantly exposed to micromembrane lesions. Depending on the severity, these damages are restored using various complexes. One of the main reparative complexes is the dysferlin-dependent mechanism. Mutations can lead to a defect in the membrane repair, causing the influx of Ca 2+ into the cell, which leads to a cell`s destruction. There are three genetically identifiable types of Miyoshi myopathy: MMD1, MMD2, MMD3. The main clinical signs of the disease are the muscle weakness and atrophy, with predominant involvement of the distal parts of the lower limbs, especially in the gastrocnemius and plantar muscles. The MM causes tip toe walking disturbances and difficulties in climbing the stairs. Progression of the disease and further atrophy leads to the wasting of the lower girdle muscles, mainly gluteal ones. Peculiarity of these myopathies is the absence of cardiomyopathy, due to the immunity of cardiomyocytes to a deficiency of the protein dysferelin. Diagnosis is made on the basis of muscle biopsy and molecular genetic testing. The gold standard is immunoblotting or immunohistochemistry. One of treatment methods is the use of improperly folded dysferlin (treatment with a proteasome inhibitor MG-132) in fibroblasts with restoration of membrane sealing. The aim of this case report is to present an example of a possible clinical diagnosis of MM in a young man, in the absence of opportunities for molecular genetic testing.

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Molecular Genetic Testing for Acute Myeloid Leukemia

Klinicka onkologie ◽

10.14735/amko2016411 ◽

2016 ◽

Vol 29 (6) ◽

pp. 411-418 ◽

Cited By ~ 1

Author(s):

Veronika Janečková ◽

Lukáš Semerád ◽

Ivana Ježíšková ◽

Dana Dvořáková ◽

Martin Čulen ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Genetic Testing ◽

Myeloid Leukemia ◽

Molecular Genetic ◽

Molecular Genetic Testing ◽

Acute Myeloid

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PERSONALIZED MEDICINE: FROM SCIENCE TO PRACTICE

Clinical Practice ◽

10.17816/clinpract7473-74 ◽

2016 ◽

Vol 7 (4) ◽

pp. 73-74

Author(s):

A G Nikitin

Keyword(s):

Genetic Testing ◽

Personalized Medicine ◽

Early Diagnosis ◽

Molecular Genetic ◽

Genomic Data ◽

Routine Practice ◽

Molecular Genetic Testing ◽

Federal Research ◽

Modern Methods ◽

Clinical Centre

In 2012, in Federal research and clinical centre of FMBA of Russia the laboratory of genetics was established, which conducts scientific research in the field of genetic predisposition to socially significant diseases, early diagnosis of oncopathology, as well as methods for processing genomic data. Significant experience in molecular genetic testing have allowed to help to implement a routine practice of a multiprofile hospital modern methods of genetic analysis that were previously available only to large specialized centers.

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