Mehveş PODA, Filiz GÜÇLÜ GEYİK, Neslihan Çoban, Beyhan Tüysüz, Gamze Güven, Evrim Kömürcü Bayrak, Nihan Erginel Unaltuna

Evaluation of dystrophin gene deletion patterns in a large Duchenne/Becker muscular dystrophy patient sample; 17 years experience from one Turkish Diagnostic Center

Duchenne/Becker muscular dystrophy (DMD/BMD) is an X-linked recessive disease results from mutations in the dystrophin gene. We established the deletion pattern profile in unrelated DMD/BMD patients using multiplex PCR (M-PCR). Methods: During 1998-2015, 1,385 unrelated DMD/BMD patients were admitted for genetic conﬁrmation and/or exclusion of the disease. Deletion analysis in the dystrophin (DMD) gene was performed. Results: Of all patients admitted, 42.6 % deletion carriers (n=589) were detected, of which 180 (80.3 %) were carrying single exon deletions and 409 (14.8 %) multiple exon deletions. Deletions covering the major hotspot region were 80.3 %, the minor region 14.8% and 2.4% covered both regions. The mean age of diagnosis of patients with out-of-frame deletions (7.27 year) was notably lower than the cases with in frame deletions (17.54 year). No single exon 4 deletion was detected. Conclusions: When the known deletion hotspots are considered, the study population showed a similar deletion pattern with other populations. The mean age of patients with out-of-frame deletions were lower than mean age of those with in-frame deletions, in concordance with the reading frame hypothesis. Strikingly, no single exon 4 deletion was found, supporting the hypothesis that absence of it might have no functional consequences.

Anahtar Kelimeler:

Dystrophin, Gene Deletion, Duchenne-Becker Muscular Dystrophy

Evaluation of dystrophin gene deletion patterns in a large Duchenne/Becker muscular dystrophy patient sample; 17 years experience from one Turkish Diagnostic Center

Background: Duchenne/Becker muscular dystrophy (DMD/BMD) is an X-linked recessive diseaseresults from mutations in the dystrophin gene. We established the deletion pattern profile in unrelatedDMD/BMD patients using multiplex PCR (M-PCR). Methods: During 1998-2015, 1,385 unrelatedDeletionanalysis in the dystrophin(DMD) gene was performed.Results: Of all patients admitted, 42.6% deletioncarriers (n=589) were detected, of which 180 (80.3 %)were carrying single exon deletions and 409 (14.8%) multiple exon deletions. Deletions covering the major hotspot region were 80.3 %, the minor region14.8% and 2.4% covered both regions. The mean age of diagnosis of patients with out-of-framedeletions (7.27 year) was notably lower than the cases with in frame deletions (17.54 year). No singleexon 4 deletion was detected.Conclusions: When the known deletion hotspots are considered, thestudy population showed a similar deletion pattern with other populations. The mean age of patients without-of-frame deletions were lower than mean age of those with in-frame deletions, in concordance withthe reading frame hypothesis. Strikingly, no single exon 4 deletion was found, supporting the hypothesisthat absence of it might have no functional consequences

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