AİLESEL HİPERTROFİK KARDİYOMİYOPATİDE SARKOMERİK GEN VARYANTLARININ ANİ KARDİYAK ÖLÜM RİSKİNİN ÖNGÖRÜLMESİNE KATKISI

Öz

Amaç: Hipertrofik kardiyomiyopati (HKM), ani kardiyak ölümün (AKÖ) nedenlerinden biridir. Bu çalışmada, HKM’de en sık mutasyon bulunan üç sarkomerik gende, AKÖ için yüksek riskli patojenik varyantların belirlenmesi amaçlandı. Gereç ve Yöntem: Çalışmaya, AKÖ ve/veya HKM için aile öyküsü olan 12 yetişkin HKM’li indeks vaka ve 31 aile üyesi dahil edildi. Tüm katılımcılar, kardiyolojik olarak değerlendirildi. MYH7, MYBPC3 ve TNNT2 genlerinin ekzonik bölgeleri, CorTAG HCM1 dizileme sistemi kullanılarak analiz edildi. Bulgular: HKM’li indeks vakaların 8’inde, amino asit değişimine neden olan 6 farklı patojenik varyant bulundu. Bunlardan beşinin, MYH7 genindeki Val698Ala, Arg719Trp, Met822Leu ve Arg- 663Cys (üç vakada) ve TNNT2 genindeki Arg102Trp değişimlerinin daha önce tanımlanmış yanlış anlamlı patojenik varyantlar olduğu belirlendi. İleri yaşta AKÖ öyküsü olan bir HKM ailesinde, MYBPC3 geninde Tyr525Asn ve c.*27-21G>A varyantlar bileşik heterozigot olarak ilk defa tanımlandı. Bu varyantlar, Türk popülasyonu kontrol örneklerinde (n=777) saptanmadı. Sonuç: Bu çalışmada, AKÖ öyküsü olan bir HKM ailesinde yeni varyantlar tanımlandı. Ancak, HKM ailelerinde saptanan patojenik varyantlar ile AKÖ riski arasında net bir ilişki bulunamadı.

Anahtar Kelimeler

• Sarkomerik gen varyantı
• ailesel hipertrofik kardiyomiyopati
• ani kardiyak ölüm

CONTRIBUTION OF SARCOMERIC GENE VARIANTS TO THE PREDICTION OF SUDDEN CARDIAC DEATH RISK IN FAMILIAL HYPERTROPHIC CARDIOMYOPATHY

Öz

Objective: Hypertrophic cardiomyopathy (HCM) is one of sudden cardiac death (SCD) causes. This study aimed to identify high-risk pathogenic variants for SCD in the three sarcomeric genes with the most frequent mutations in HCM. Material and Method: The study included 12 adult HCM index cases with a family history of SCD and/or HCM, and 31 of their family members. All the participants were evaluated with detailed cardiac examinations. The exonic regions of the MYH7, MYBPC3 and TNNT2 genes were analysed using CorTAG HCM1 resequencing arrays. Results: Six pathogenic variants causing amino acid substitutions were found in 8 of the index cases with HCM. Five of them were identified as previously defined missense variants of Val698Ala, Arg719Trp, Met822Leu and Arg663Cys (in three cases) in the MYH7 gene, and Arg102Trp in the TNNT2 gene. For the first time in an HCM family with a history of late-onset SCD, Tyr525Asn and c.*27-21G> A variants in the MYBPC3 gene were identified as compound heterozygous. These variants were not present in control subjects (n=777) from the Turkish population. Conclusion: In this study, novel variants in the MYBPC3 gene were identified in an HCM family with SCD history. However, there was no clear association between pathogenic variants and the risk of SCD.

Anahtar Kelimeler

• Sarcomeric gene variant
• familial hypertrophic cardiomyopathy
• sudden cardiac death

Kaynakça

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