open access

Vol 47, No 2 (2013)
ARTYKUŁ ORYGINALNY
Submitted: 2012-02-27
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Two mutations in one dystrophin gene

Janusz Zimowski, Elżbieta Fidziańska, Mariola Holding, Jacek Zaremba
DOI: 10.5114/ninp.2013.34586
·
Neurol Neurochir Pol 2013;47(2):131-137.

open access

Vol 47, No 2 (2013)
ARTYKUŁ ORYGINALNY
Submitted: 2012-02-27

Abstract

Background and purpose

Duchenne/Becker muscular dystrophies (DMD/BMD) lead to progressive irreversible muscle deterioration caused by recessive mutations in the dystrophin encoding gene (Xp21.1). Approximately 60% of mutations are deletions, 10% are duplications and the remaining 30% are point mutations. The aim of the study is to present the rare occurrence of two pathogenic mutations (deletions or duplications) in one allele of the dystrophin gene.

Material and methods

DNA of patients from 1364 DMD/BMD families was tested. Two techniques – PCR-multiplex and multiplex ligation-dependent probe amplification – were used to search for mutations in the dystrophin gene.

Results

Deletion was detected in 648 families and duplication was found in 74 families (analysis in progress). In two families, presence of two mutations in one gene was documented – in the first family two deletions were found (exons 45–49 and 60–61), and in the second family two duplications were detected (exons 2–7 and 50–59). One of the deletions disrupted the reading frame, and the other deletion retained the reading frame. Both duplications also retained the reading frame of the gene but in both families the disease took a severe course (DMD). In the family with two duplications prenatal diagnosis was also carried out, and carriership of both mutations was discovered in the female fetus.

Conclusions

In the analyzed group of DMD/BMD families, the frequency of combined occurrence of two mutations in one gene was 2 per 722 (0.3%). The phenomenon of detected non-contiguous deletions and duplications is presented together with 31 similar cases published so far.

Abstract

Background and purpose

Duchenne/Becker muscular dystrophies (DMD/BMD) lead to progressive irreversible muscle deterioration caused by recessive mutations in the dystrophin encoding gene (Xp21.1). Approximately 60% of mutations are deletions, 10% are duplications and the remaining 30% are point mutations. The aim of the study is to present the rare occurrence of two pathogenic mutations (deletions or duplications) in one allele of the dystrophin gene.

Material and methods

DNA of patients from 1364 DMD/BMD families was tested. Two techniques – PCR-multiplex and multiplex ligation-dependent probe amplification – were used to search for mutations in the dystrophin gene.

Results

Deletion was detected in 648 families and duplication was found in 74 families (analysis in progress). In two families, presence of two mutations in one gene was documented – in the first family two deletions were found (exons 45–49 and 60–61), and in the second family two duplications were detected (exons 2–7 and 50–59). One of the deletions disrupted the reading frame, and the other deletion retained the reading frame. Both duplications also retained the reading frame of the gene but in both families the disease took a severe course (DMD). In the family with two duplications prenatal diagnosis was also carried out, and carriership of both mutations was discovered in the female fetus.

Conclusions

In the analyzed group of DMD/BMD families, the frequency of combined occurrence of two mutations in one gene was 2 per 722 (0.3%). The phenomenon of detected non-contiguous deletions and duplications is presented together with 31 similar cases published so far.

Get Citation

Keywords

non-contiguous deletions, non-contiguous duplications, Duchenne muscular dystrophy, Becker muscular dystrophy, multiplex ligation-dependent probe amplification

About this article
Title

Two mutations in one dystrophin gene

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 47, No 2 (2013)

Pages

131-137

DOI

10.5114/ninp.2013.34586

Bibliographic record

Neurol Neurochir Pol 2013;47(2):131-137.

Keywords

non-contiguous deletions
non-contiguous duplications
Duchenne muscular dystrophy
Becker muscular dystrophy
multiplex ligation-dependent probe amplification

Authors

Janusz Zimowski
Elżbieta Fidziańska
Mariola Holding
Jacek Zaremba

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