Molecular Genetic Approaches in Diagnosis of Duschenne/ Becker Muscular Dystrophy
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Date
2020
Authors
Bayanova, M.
Uahit, R.
Tolegen, N.
Nazarova, L.
Abilkhadirova, A.
Khamzina, A.
Nauryzbaeva, A.
Jaxybayeva, A.
Journal Title
Journal ISSN
Volume Title
Publisher
International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana
Abstract
Introduction: Duchenne/Becker muscular dystrophy (DMD/BMD) is inherited X-linked disease with a
frequency of 1: 3,500 newborn males. Deletions and duplications in the DMD gene are errors of reading
frameshift and premature termination of translation. Structural rearrangements of BMD does not lead
to reading frame rule, DNA polymerase can “skip” deleted exons , which leads to the synthesis of truncated
protein, which can fulfill its functions some extent.
Methods: We studied the DNA of 104 patients with suspected DMD / BMD and heterozygous, as well
as chorionic villi samples (CVS) obtained by prenatal diagnostics. Multiplex Ligation - dependent Probe
Amplification(MLPA) (MRC Holland) was used to study of copy number variations of 79 exons of DMD
gene. Validation MLPA results and whole exome sequencing (WES) of patients with MLPA negative results
were performed at Centogene (Germany). Detection of nonsense mutations leading to the appearance
in mRNA a premature stop codons of DMD gene are relevant to stratify patients for antisense-targeted
therapy of Duchenne muscular dystrophy.
Results: Mutations of (36) 37 % of patients were revealed in the DMD gene. Deletions were detected
in (27) 75 %, duplications in (9) 25% of cases. WES of 41patients was conducted for validation and MLPA
negative results. Point mutations were identified in 30 (73%), frameshift missense mutations - in 7 (23%),
nonsense mutations - in 9 (30 %) cases. Validation of MLPA results (deletions) were performed in 14 patients
(46 %).
Conclusions: Algorithm of molecular diagnostic of DMD /BMD by MLPA is a method for the detection of
large deletions and duplications 79 exons of DMD gene and WES should be to determine the missense
and nonsense mutations of DMD gene. Our results formed the basis of clinical protocols of diagnostic
and treatment of Duchenne/Becker muscular dystrophy in Kazakhstan.
Description
Keywords
Duchenne/Becker muscular dystrophy, mutations, MLPA, Research Subject Categories::MEDICINE