DMD/BMD Hastalarında Genetik Spektrum: Tek Merkezden MLPA ve Sanger Sonuçları

Öz

Amaç: Duchenne ve Becker Musküler Distrofi (DMD/BMD), distrofin proteinini kodlayan DMD genindeki değişimlere bağlı olarak gelişen, ilerleyici kas güçsüzlüğü ve kaybı ile seyreden X’e bağlı resesif kalıtılan bir nöromüsküler hastalıktır. Bu çalışmanın amacı, genetik analiz ile DMD geninde varyant saptanmış ve DMD/BMD tanısı almış olguların genetik ve klinik özelliklerini değerlendirmektir. Materyal ve metot: Bu retrospektif çalışmada, DMD geni analizi ile moleküler tanısı doğrulanmış 32 aileden 34 erkek DMD/BMD olgusu (DMD tanısı alan 24 olgu (%70,6) ve BMD tanısı alan 10 (%29,4) olgu) değerlendirildi. Klinik, biyokimyasal ve aile öyküsü verileri hasta dosyalarından elde edildi. Hastaların genetik analizleri çoklu ligasyon bağımlı prob amplifikasyonu (MLPA) ve Sanger dizileme yöntemleriyle gerçekleştirilmişti. 15 anneden taşıyıcılığa yönelik segregasyon analizi yapılmıştı. Bulgular: Olguların %79,4’ünde ekzon delesyonu, %20,6’sında küçük varyant tespit edildi. En sık delesyon bölgeleri 45-52. ekzonlar arasındaydı. CK düzeyleri tüm hastalarda yüksek saptanmıştı. Ortalama tanı yaşı 5’ti. Segregasyon analizi yapılan annelerden 12 tanesinin çocuğunda saptanan varyantı taşıdığı gösterilmişti. Kohortumuzda daha önce literatürde bildirilmemiş 3 yeni varyant saptanmıştır. Sonuç: DMD/BMD olgularında genetik analizler tanı koymada, fenotipik öngörüde bulunmada ve aile taramasında oldukça değerlidir. Bu çalışmada, Türkiye’den bildirilen olgulara katkı sağlayacak şekilde, DMD/BMD’ye neden olan varyant tipleri ve klinik özellikler ortaya konmuştur. Moleküler tanının etkin kullanımı, erken tanı ve yönetim için önem taşımaktadır.

Anahtar Kelimeler

• DMD
• BMD
• MLPA
• Sanger dizileme
• Novel varyant

Genetic Profile of DMD/BMD: MLPA and Sanger Sequencing Results from a Single Center

Öz

Background: Duchenne and Becker Muscular Dystrophy (DMD/BMD) is an X-linked recessive inherited neuromuscular disease characterised by progressive muscle weakness and wasting due to variants in the DMD gene encoding dystrophin protein. This study aimed to evaluate the genetic and clinical characteristics of patients diagnosed with DMD/BMD who were found to have variants in the DMD gene by genetic analysis. Material and Methods: In this retrospective study, we evaluated 34 patients from 32 families diagnosed with dystrophinopathies, including 24 individuals (70.6%) with DMD and 10 individuals (29.4%) with BMD. Clinical, biochemical, and family history data were obtained from patient files. Genetic analyses were performed by multiple ligation-dependent probe amplification (MLPA) and Sanger sequencing. 15 mothers were segregated for carriage. Results: Exon deletion was detected in 79.4% of cases, and a small variant in 20.6%. The most common deletion sites were between exons 45-52. CK levels were found to be high in all patients. The mean age at diagnosis was 5 years. Segregation analysis showed that 12 of the mothers carried the variant detected in their children. Three new variants that had not been reported in the literature before were found in our cohort. Conclusions: Genetic analyses are valuable in diagnosis, phenotypic prediction, and family screening in DMD/BMD cases. In this study, the variant types and clinical features of DMD/BMD were analysed to contribute to the reported cases from Türkiye. Effective use of molecular diagnosis is important for early diagnosis and management.

Anahtar Kelimeler

• DMD
• BMD
• MLPA
• Sanger sequencing
• Novel variants

Kaynakça

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