title: MLPA based detection of mutations in the dystrophin gene of 180 Polish families with Duchenne/Becker muscular dystrophy.
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.
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland. Electronic address: zimowski@ipin.edu.pl.
authors.forename: Janusz G
authors.initials: JG
authors.lastname: Zimowski
authors.affiliation: I Department of Obstetrics and Gyneacology, Centre of Postgraduate Medical Education, Warsaw, Poland.
authors.forename: Diana
authors.initials: D
authors.lastname: Massalska
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Mariola
authors.initials: M
authors.lastname: Holding
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Jadczak
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Fidziańska
authors.affiliation: Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lusakowska
authors.affiliation: Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kostera-Pruszczyk
authors.affiliation: Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kamińska
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Zaremba
mesh_terms: D016189:Dystrophin / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D020440:Gene Duplication; D006579:Heterozygote; D006801:Humans; D008297:Male; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D017354:Point Mutation; D011044:Poland
chemical_list: C484258:DMD protein, human; D016189:Dystrophin
keywords: Duchenne/Becker muscular dystrophy; Molecular diagnostics; Multiplex ligation-dependent probe amplification