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Analysis of PMP22 duplication and deletion using a panel of six dinucleotide tandem repeats

  • Milica Gagic , Milica Keckarevic Markovic EMAIL logo , Miljana Kecmanovic , Dusan Keckarevic , Jelena Mladenovic , Jelena Dackovic , Vedrana Milic-Rasic und Stanka Romac
Veröffentlicht/Copyright: 17. Oktober 2015
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 54 Heft 5

Abstract

Background:

Charcot-Marie-Tooth type 1A (CMT1A) is the most common type of hereditary motor and sensory neuropathies (HMSN), caused by the duplication of the 17p11.2 region that includes the PMP22 gene. Reciprocal deletion of the same region is the main cause of hereditary neuropathy with liability to pressure palsies (HNPP). CMT1A accounts for approximately 50% of HMSN patients. Diagnostics of CMT1A and HNPP are based on quantitative analysis of the affected region or RFLP detection of breakage points. The aim of this study was to improve the sensitivity and efficiency of CMT1A and HNPP genetic diagnostics by introducing analysis of six STR markers (D17S261-D17S122-D17S839-D17S1358-D17S955-D17S921) spanning the duplicated region.

Methods:

Forty-six CMT1A and seven HNPP patients, all genetically diagnosed by RFLP analysis, were tested for duplication or deletion using six STR markers.

Results:

In all CMT1A and HNPP patients, microsatellite analysis comprising six STR markers confirmed the existence of a duplication or deletion. In 89% (41/46) CMT1A patients the confirmation was based on detecting three alleles on at least one locus. In the remaining 11% (5) CMT1A patients, duplication was also confirmed based on two peaks with clear dosage difference for at least two different markers. All HNPP patients (7/7) displayed only one allele for each analyzed locus.

Conclusions:

Microsatellite analysis using six selected STR loci showed a high level of sensitivity and specificity for genetic diagnostics of CMT1A and HNPP. The results here strongly suggest STR marker analysis as a method of choice in PMP22 duplication/deletion testing.

Keywords: Charcot-Marie-Tooth type 1A; genetic testing; hereditary neuropathy with liability to pressure palsies; microsatellites
Corresponding author: Milica Keckarevic Markovic, Faculty of Biology, University of Belgrade, Studentski trg 3, 11000 Belgrade, Serbia, Phone/Fax: +381 11 2639100, E-mail:
aMilica Gagic and Milica Keckarevic Markovic contributed equally to this work.

Acknowledgments

This work was supported by Serbian Ministry of Education and Science, grant no. 173016.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by Serbian Ministry of Education and Science, grant no. 173016.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2015-6-26
Accepted: 2015-9-10
Published Online: 2015-10-17
Published in Print: 2016-5-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2015-0602
Schlagwörter für diesen Artikel
Charcot-Marie-Tooth type 1A; genetic testing; hereditary neuropathy with liability to pressure palsies; microsatellites

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Protein S100B: from cancer diagnostics to the evaluation of mild traumatic brain injury
  4. Reviews
  5. Capillary electrophoresis based on nucleic acid detection for diagnosing human infectious disease
  6. Oxidative damage and the pathogenesis of menopause related disturbances and diseases
  7. Opinion Paper
  8. EFLM WG-Preanalytical phase opinion paper: local validation of blood collection tubes in clinical laboratories
  9. Genetics and Molecular Diagnostics
  10. Effective quality management practices in routine clinical next-generation sequencing
  11. Analysis of PMP22 duplication and deletion using a panel of six dinucleotide tandem repeats
  12. A novel exonuclease (TaqMan) assay for rapid haptoglobin genotyping
  13. General Clinical Chemistry and Laboratory Medicine
  14. Heparinate but not serum tubes are susceptible to hemolysis by pneumatic tube transportation
  15. Criteria of adequacy for vitamin D testing and prevalence of deficiency in clinical practice
  16. A simple clot based assay for detection of procoagulant cell-derived microparticles
  17. Measurement of factor XIII (FXIII) activity by an automatic ammonia release assay using iodoacetamide blank-procedure: no more overestimation in the low activity range and better detection of severe FXIII deficiencies
  18. Immunoassay or LC-MS/MS for the measurement of salivary cortisol in children?
  19. Head to head evaluation of the analytical performance of two commercial methotrexate immunoassays and comparison with liquid chromatography-mass spectrometry and the former fluorescence polarization immunoassay
  20. Reference Values and Biological Variations
  21. Preanalytical, analytical, gestational and pediatric aspects of the S100B immuno-assays
  22. Establishment of reference intervals of clinical chemistry analytes for the adult population in Saudi Arabia: a study conducted as a part of the IFCC global study on reference values
  23. First data on the biological variation and quality specifications for plasma ammonia concentrations in healthy subjects
  24. Cancer Diagnostics
  25. Hypermethylation of DLX4 predicts poor clinical outcome in patients with myelodysplastic syndrome
  26. Cardiovascular Diseases
  27. Galectin-3, osteopontin and successful aging
  28. Platelet volume is associated with the Framingham risk score for cardiovascular disease in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
  29. Infectious Diseases
  30. Diagnostic values of CD64, C-reactive protein and procalcitonin in ventilator-associated pneumonia in adult trauma patients: a pilot study
  31. Corrigendum
  32. Corrigendum to: Accuracy of GFR estimating equations combining standardized cystatin C and creatinine assays: a cross-sectional study in Sweden
  33. Letters to the Editor
  34. Theranos phenomenon – part 3
  35. Biological variation of high sensitivity cardiac troponin-T in stable dialysis patients: implications for clinical practice
  36. Biological variation of high sensitivity cardiac troponin-T in stable dialysis patients: implications for clinical practice
  37. Impact of specimen mixing methods on presepsin point-of-care test results using whole blood
  38. Clinical laboratories have a critical role in test strip lot management in glucose point-of-care testing
  39. Hemoglobin A2-Leuven (α2δ2 143(H21) His>Asp): a novel delta-chain variant potentially interfering in hemoglobin A1c measurement using cation exchange HPLC
  40. Eryptosis is induced by hyperthermia in hereditary spherocytosis red blood cells
  41. Investigation of sensitivity for coagulation factor deficiency in APTT and PT: how to perform it?
  42. Underestimation of hepcidin concentration by time of flight mass spectrometry and competitive ELISA in hepcidin p.Gly71Asp heterozygotes
  43. Congress Abstracts
  44. ISMD2016 Eleventh International Symposium on Molecular Diagnostics
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