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Analysis of dystrophin gene in Iranian Duchenne and Becker muscular dystrophies patients and identification of a novel mutation

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Abstract

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are the most frequent muscular dystrophies. Present study aimed to determine the frequency of dystrophin gene alterations in Iranian DMD/BMD patients using molecular techniques. 146 Iranian DMD/BMD patients have been analyzed using two devised sets of multiplex polymerase chain reaction (M-PCR) followed by multiple ligation-dependent probe amplification (MLPA). Two isolated DMD and BMD patients were analyzed by DNA sequencing. 30.9 % of patients had single-exon deletion while group and contiguous exon deletions were identified in 41 % of the patients. The most numerous exon deletions included exons 45–50 and were identified in the first M-PCR set. Deletion detection rate was 99 % in first M-PCR set and remaining deletions (1 %) were identified in the second M-PCR set. MLPA analysis showed that there were two exons 3–5 and 41–43 duplications (1.4 %) in a BMD and a DMD patient, respectively. Two nonsense mutations including c.633dupA and c.6283 C>T were, respectively, found in a DMD and BMD patient in which c.633dupA has not ever been reported in DMD mutation database and was pathogenic mutation. Besides the report of frequency of dystrophin gene alteration in a subset of Iranian DMD/BMD patients, it was revealed that the proposed M-PCR protocol can be useful in the initial step of molecular diagnosis of DMD/BMD. Exon sequencing would be the final step in determining the mutation status of DMD/BMD patients following MLPA.

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Abbreviations

ABD1:

Actin-binding domain 1

BMD:

Becker muscular dystrophy

CPK:

Creatine phosphokinase

DMD:

Duchene muscular dystrophy

EMG:

Electromyography

FISH:

Fluorescent in situ hybridization

IHC:

Immunohistochemistry

M-PCR:

Multiplex polymerase chain reaction

MAPH:

Multiplex amplifiable probe hybridization

PND:

Prenatal diagnosis

RPA:

Relative peak area

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Acknowledgments

There is no commercial or proprietary interest in any drug, device, or equipment mentioned in this article.

Conflict of interest

No conflict of interest.

Ethical standard

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Authors and Affiliations

  1. Department of Neurology, Children’s Medical Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Gholam Reza Zamani

  2. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Fatemeh Karami & Mahdi Zamani

  3. Department of Pediatric Hematology and Oncology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mahshid Mehdizadeh

  4. Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Abolfazl Movafagh

  5. Pediatric Pathology Research Center, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Yalda Nilipour

  6. Department of Neurogenetics, Iranian Center of Neurological Research, Tehran University of Medical Sciences, 1417613151, Tehran, Iran

    Gholam Reza Zamani & Mahdi Zamani

Authors
  1. Gholam Reza Zamani
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  2. Fatemeh Karami
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  3. Mahshid Mehdizadeh
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  4. Abolfazl Movafagh
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  5. Yalda Nilipour
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  6. Mahdi Zamani
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Correspondence to Mahdi Zamani.

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Zamani, G.R., Karami, F., Mehdizadeh, M. et al. Analysis of dystrophin gene in Iranian Duchenne and Becker muscular dystrophies patients and identification of a novel mutation. Neurol Sci 36, 2011–2017 (2015). https://doi.org/10.1007/s10072-015-2290-2

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  • DOI: https://doi.org/10.1007/s10072-015-2290-2

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