Gorlin Sendromlu olgularda saptanan üç yeni PTCH1 varyantı

Amaç: Gorlin Sendromu (OMIM #109400), bazal hücreli karsinomalar (BHK), iskelet anomalileri ve çenede gözlenen çok sayıdaki kistlerle karakterize otozomal dominant kalıtımlı nadir bir hastalıktır. Gorlin Sendromunun %50-85’inden PTCH1 genindeki mutasyonlar sorumludur. Bu çalışmada klinik olarak Gorlin Sendromu tanısı düşünülen hastalarda yapılmış PTCH1 gen dizi analizlerinin retrospektif olarak değerlendirilmesi ve varyant saptanan hastalarda fenotip-genotip korelasyonu yapılması amaçlanmıştır. Gereç ve Yöntem: Ege Üniversitesi Tıp Fakültesi Hastanesi Tıbbi Genetik Anabilim Dalı’na başvuran Gorlin Sendromu düşünülen dört hastanın PTCH1 genindeki varyantlar ile klinik ve laboratuvar bulguları geriye dönük olarak incelenmiştir. Bulgular: PTCH1 gen dizi analizi yapılan dört hastada üçü yeni olmak üzere dört farklı varyant saptanmıştır. Hastalardaki klinik bulguların sıklıkları ve dağılımı değerlendirildi. Sonuç: Bu çalışma Türkiye’de yapılan Gorlin Sendromlu olgularda PTCH1 gen varyantlarının dağılımı ile ilgili ilk çalışma olup üç yeni varyant saptanmıştır. Saptanan varyantlar ve klinik bulgular ile fenotip-genotip korelasyonu değerlendirilmiştir.

Detection of three new PTCH1 variants in patients with Gorlin Syndrome

Aim: Gorlin Syndrome (OMIM # 109400) is a rare autosomal dominant disease characterized by basal cell carcinomas (RCC), skeletal abnormalities and multiple cysts observed in the jaw. Mutations in the PTCH1 gene are responsible for 50-85% of Gorlin Syndrome. The aim of this study was to retrospectively evaluate PTCH1 gene sequence analysis in patients with clinically diagnosed Gorlin Syndrome and to delineate phenotype-genotype correlations. Materials and Methods: Four patients who referred to the Ege University Medical Faculty Hospital Medical Genetics Department due to Gorlin Syndrome were considered with mutations in PTCH1 gene and clinical findings analyzed retrospectively. Results: Four different mutations mutations (with three being novel) were detected in four patients who underwent PTCH1 gene sequence analysis. The frequency and distribution of clinical findings were evaluated. Conclusion: This is the first study from Turkey investigating PTCH1 gene mutation spectrum in Gorlin Syndrome which were identified three novel mutations. Phenotype-genotype correlation was evaluated with mutations and clinical findings.

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