Molecular and clinical evaluation in an extensive family with becker muscular dystrophy

Yıl 2010, Cilt: 41 Sayı: 4, 213 - 216, 01.05.2010

Esra Tuğ Halil İbrahim Atasoy Hatip Aydın Zeynep Ocak

Öz

Objective: Becker Muscular Dystrophy (BMD) often results from in-frame mutations of the dystrophin gene that allows production ofcm altered but partially functional protein. A 9-year-old boy was referred for evaluation because of elevated serum creatine kinase (CK) activity, during routine blood screening for hypospadias surgery. Because of blood screening of the proband's older brother (11-year-old) showed elevated CK activity and there are muscle weakness findings together with elevated CK activity in 2nd, 3rd and fifth degree relatives of proband, we planned molecular analysis for dystrophin gene to proband and his brother. Material and Methods: Molecular genetics analysis was undertaken for exons 3, 4, 8, 12, 17, 19, 32, 34, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 and 52 in the dystrophin gene of the proband and his brother. Multiplex PCR was undertaken with the extracted DNA, and the products were run on an agarose gel. Results: This molecular work-up showed the proband and his brother to be carriers of a deletion implying exons 13-19 of the dystrophin gene. Family members showing elevated CK activity and were aged between 9-25 yrs, had no clinical symptoms at all. 40-years-old maternal uncle of the proband showed mild muscle weakness and 60-years-old maternal grand uncle showed severe muscle weakness. Conclusion: Based on molecularfindings, this family would be given a diagnosis of BMD. This diagnosis implies the development of clinical symptoms, even though this family is clearly asymptomatic for the first decades. This report show that there are early diagnostic significance of detailed family inquiry and practised molecular analyses by inspiring biochemical indicators in presymptomatic BMD cases.

Anahtar Kelimeler

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Becker musküler distrofili geniş bir ailede moleküler ve klinik değerlendirme

Öz

Amaç: Becker Müsküler Distrofi (BMD), sıklıkla distrofin geni içindeki fonksiyonel proteinin kısmen değişmesine neden olan mutasyonlar sonucu oluşur. Hipospadias nedeniyle cerrahi operasyon planlanan 9 yaşında bir erkek çocuk rutin kan testleri sırasında artmış serum kreatin kinaz (CK) aktivitesi nedeniyle değerlendirilmek üzere kliniğimize sevk edildi. Probandın 11 yaşındaki kardeşinin serumunda yüksek CK tespit edilmesi ve 2., 3. ve 5. dereceden akrabalarında yüksek CK ve kas güçsüzlüğü bulgularının olması nedeniyle probanda ve kardeşine distrofin geninin moleküler analizi yapılması planlandı. Yöntem: Probanda ve erkek kardeşine distrofin geninin 3, 4, 8, 12, 17,19, 32, 34, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 ve 52 ekzonları için moleküler genetik analiz yapıldı. DNA 'larının izolasyonu sonrasında multipleks PCR uygulandı ve ürünler agaroz jelde görüntülendi. Bulgular: Bu moleküler analiz ile, probandın ve erkek kardeşinin distrofin geninin 13-19 ekzonlarını içeren bir delesyon taşıyıcısı oldukları gösterildi. Yaş ortalamaları 9-25 arasında değişen ve artmış CK aktivitesi gösteren aile üyelerinin hiçbirinde klinik bulgu mevcut değildi. Probandın 40 yaşında olan dayısı orta derecede kas güçsüzlüğü, annesinin dayısı (60) ise ciddi kas güçsüzlüğü göstermekteydi. Sonuçlar: Moleküler bulgulara dayanılarak, klinik semptomların gelişimi BMD tanısı ile açıklanabilir; ayrıca, ailenin ilk dekadlarda asemptomatık olduğu söylenebilir. Bu rapor, presemptomatik BMD vakalarında, biyokimyasal belirteçler ışığında yapılan moleküler çalışmalar ve ayrıntılı ailesel sorgulanmaların erken tanısal değerini ortaya koymaktadır.

Anahtar Kelimeler

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Kaynakça

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