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Investigation of genotype-phenotype and familial features of Turkish dystrophinopathy patients

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Abstract

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive allelic muscle diseases caused by dystrophin gene mutations. Eight hundred thirty-seven patients admitted between 1997 and 2022 were included in the study. Two hundred twenty patients were analyzed by multiplex PCR (mPCR) alone. Five hundred ninety-five patients were investigated by multiplex ligation-dependent probe amplification (MLPA), and 54 patients were examined by sequencing. Deletion was detected in 60% (132/220) of the cases in the mPCR group only and in 58.3% (347/595) of the cases with MLPA analysis. The rates of deletion and duplication were 87.7% and 12.3%, respectively, in the MLPA analysis. Single exon deletions were the most common mutation type. The introns 43–55 (81.8%) and exons 2–21 (13.1%) regions were detected as hot spots in deletions. It was determined that 89% of the mutations were suitable for exon skipping therapy. The reading frame rule did not hold in 7.6% of D/BMD cases (17/224). We detected twenty-five pathogenic/likely pathogenic variants in sequencing, five of which were novel variants. Nonsense mutation was the most common small mutation (44%). 21% of DMD patients were familial. We detected germline mosaicism in four families (4.3%) in the large rearrangement group and one gonosomal mosaicism in a family with a nonsense mutation. This is the largest study examining genotype and phenotype data in Turkish D/BMD families investigated by MLPA analysis. The reading frame hypothesis is not valid in all cases. Sharing the genotype and phenotype characteristics of these cases in the literature will shed light on the molecular structure of DMD and guide gene therapy research. In genetic counseling, carrier screening in the family and possible gonadal mosaicism should be emphasized.

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Authors and Affiliations

  1. Department of Medical Genetics, Faculty of Medicine, Dokuz Eylul University, Izmir, 35340, Turkey

    Hande Ozkalayci, Elcin Bora, Tufan Cankaya, Mehmet Kocabey, Nadide Cemre Zubari, Ahmet Okay Caglayan & Ayfer Ulgenalp

  2. Department of Pediatric Neurology, Faculty of Medicine, Dokuz Eylul University, Izmir, 35340, Turkey

    Uluc Yis

  3. Department of Pediatric Genetics, Faculty of Medicine, Dokuz Eylul University, Izmir, 35340, Turkey

    Ozlem Giray Bozkaya

  4. Department of Child And Adolescent Psychiatry, Faculty of Medicine, Dokuz Eylul University, Izmir, 35340, Turkey

    Serkan Turan & Aynur Pekcanlar Akay

  5. Department of Medical Genetics, Istanbul Training and Research Hospital, Istanbul, 34146, Turkey

    Hande Ozkalayci

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  1. Hande Ozkalayci
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Correspondence to Hande Ozkalayci.

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This study was approved by the Dokuz Eylul University Ethics Committee (Decision No:2017/28–32). Additionally, 28 patients between the ages of 6 and 18, who accepted the study, were referred to child psychiatry for the evaluation of any psychopathology. This study was approved by the Dokuz Eylul University Ethics Committee (Decision No:2019/01-192). They were performed in accordance with the ethical standards laid down in the Declaration of Helsinki.

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Ozkalayci, H., Bora, E., Cankaya, T. et al. Investigation of genotype-phenotype and familial features of Turkish dystrophinopathy patients. Neurogenetics 25, 201–213 (2024). https://doi.org/10.1007/s10048-024-00765-9

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