open access

Vol 48, No 6 (2014)
Original research articles
Submitted: 2014-04-23
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MLPA based detection of mutations in the dystrophin gene of 180 Polish families with Duchenne/Becker muscular dystrophy

Janusz G. Zimowski, Diana Massalska, Mariola Holding, Sylwia Jadczak, Elżbieta Fidziańska, Anna Łusakowska, Anna Kostera-Pruszczyk, Anna Kamińska, Jacek Zaremba
DOI: 10.1016/j.pjnns.2014.10.004
·
Neurol Neurochir Pol 2014;48(6):416-422.

open access

Vol 48, No 6 (2014)
Original research articles
Submitted: 2014-04-23

Abstract

Duchenne/Becker muscular dystrophy (DMD/BMD) is a recessive, X-linked disorder caused by a mutation in the dystrophin gene. Deletions account for approximately 60–65% of mutations, duplications for 5–10%. The remaining cases are mainly point mutations. According to Monaco theory clinical form of the disease depends on maintaining or disrupting the reading frame. The purpose of the study was to determine frequency and location of deletions and duplications in the dystrophin gene, to determine the compliance between maintaining/disrupting the reading frame and clinical form of the disease and to check the effectiveness of MLPA (multiplex ligation-dependent probe amplification) in the detection of these mutations in hemizygous patients and heterozygous female carriers. The material is composed of combined results of molecular diagnosis carried out in years 2009–2012 in 180 unrelated patients referred with the diagnosis of DMD/BMD tested by use of MLPA. We identified 110 deletions, 22 duplication (in one patient two different duplications were detected) and 2 point mutations. Deletions involved mainly exons 45–54 and 3–21, whereas most duplications involved exons 3–18. The compliance with Monaco theory was 95% for deletions and 76% for duplications. Most of mutations in the dystrophin gene were localized in the hot spots – different for deletions and duplications. MLPA enabled their quick identification, exact localization and determination whether or not they maintained or disrupted the reading frame. MLPA was also effective in detection of deletions and duplications in female carriers.

Abstract

Duchenne/Becker muscular dystrophy (DMD/BMD) is a recessive, X-linked disorder caused by a mutation in the dystrophin gene. Deletions account for approximately 60–65% of mutations, duplications for 5–10%. The remaining cases are mainly point mutations. According to Monaco theory clinical form of the disease depends on maintaining or disrupting the reading frame. The purpose of the study was to determine frequency and location of deletions and duplications in the dystrophin gene, to determine the compliance between maintaining/disrupting the reading frame and clinical form of the disease and to check the effectiveness of MLPA (multiplex ligation-dependent probe amplification) in the detection of these mutations in hemizygous patients and heterozygous female carriers. The material is composed of combined results of molecular diagnosis carried out in years 2009–2012 in 180 unrelated patients referred with the diagnosis of DMD/BMD tested by use of MLPA. We identified 110 deletions, 22 duplication (in one patient two different duplications were detected) and 2 point mutations. Deletions involved mainly exons 45–54 and 3–21, whereas most duplications involved exons 3–18. The compliance with Monaco theory was 95% for deletions and 76% for duplications. Most of mutations in the dystrophin gene were localized in the hot spots – different for deletions and duplications. MLPA enabled their quick identification, exact localization and determination whether or not they maintained or disrupted the reading frame. MLPA was also effective in detection of deletions and duplications in female carriers.

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Keywords

Duchenne/Becker muscular dystrophy, Molecular diagnostics, Multiplex ligation-dependent probe amplification

About this article
Title

MLPA based detection of mutations in the dystrophin gene of 180 Polish families with Duchenne/Becker muscular dystrophy

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 48, No 6 (2014)

Pages

416-422

DOI

10.1016/j.pjnns.2014.10.004

Bibliographic record

Neurol Neurochir Pol 2014;48(6):416-422.

Keywords

Duchenne/Becker muscular dystrophy
Molecular diagnostics
Multiplex ligation-dependent probe amplification

Authors

Janusz G. Zimowski
Diana Massalska
Mariola Holding
Sylwia Jadczak
Elżbieta Fidziańska
Anna Łusakowska
Anna Kostera-Pruszczyk
Anna Kamińska
Jacek Zaremba

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