Genotype/Phenotype Correlation of Cases with PTPN11 Gene Mutation: Eastern Black Sea Experience

Abstract

Objectives: To discuss the genotype/phenotype correlation of eight cases with pathogenic variant in the PTPN11 gene. Materials and Methods: Eight cases with a prediagnosis of Noonan Syndrome, in which the PTPN11 gene sequence analysis was performed between 2017 and 2019 at Karadeniz Technical University Faculty of Medicine and Trabzon Kanuni Training and Research Hospital, Department of Medical Genetics were retrospectively evaluated in the study. Results: The most common findings in the eight cases with pathogenic variant in the PTPN11 gene were heart defect (87.5%), short stature (87.5%), and low-set posteriorly rotated ears (87.5%) and the most common heart defect was pulmonary stenosis (62.5%). The clinical diagnoses of those cases were Noonan Syndrome (87.5%) and Noonan syndrome with multiple lentigines (12.5%). NM_002834.5: PTPN11; c.922A>G; p.Asn308Asp mutation was the most commonly (25%) detected mutation. Conclusion: The phenotypes caused by all disease-causing variants found in this study were detected to be compatible with the current knowledge. Pathogenic variants of PTPN11 are responsible for 50% of RASopathies, and PTPN11 sequence analysis is a cost-effective method in patients with normal karyotyping, meeting the scoring system for Noonan Syndrome with clinical findings

Keywords

• Noonan Syndrome
• PTPN11
• Noonan Syndrome with Multiple Lentigines
• Genotype/Phenotype Correlation

PTPN11 Gen Mutasyonu Saptanan Olguların Genotip/Fenotip İlişkisi: Doğu Karadeniz Deneyimi

Abstract

Amaç: PTPN11 geninde hastalık yapıcı varyant saptanan sekiz olgunun genotip/fenotip ilişkisini tartışmak. Gereç ve Yöntem: Karadeniz Teknik Üniversitesi Tıp Fakültesi ve Trabzon Kanuni Eğitim ve Araştırma Hastanesi Tıbbi Genetik Anabilim Dalları’nda, 2017-2019 yılları arasında Noonan Sendromu ön tanısı ile PTPN11 geni dizi analizi yapılan sekiz olgu retrospektif olarak incelendi. Bulgular: PTPN11 geni patojenik varyantı saptanan sekiz olguda en sık gözlenen bulgular kalp defekti (%87,5), boy kısalığı (%87,5) ve düşük yerleşimli ve arkaya dönük kulaklar (%87,5) iken en sık rastlanan kalp defekti pulmoner stenozdu (%62,5). Olguların klinik özellikleri ise Noonan sendromu (%87,5) ve multipl lentijinli Noonan sendromu (%12,5) ile uyumlu bulundu. Çalışmada en sık rastlanan mutasyon (%25) NM_002834.5: PTPN11; c.922A>G; p.Asn308Asp idi. Sonuç: Çalışma sonucu bulunan tüm hastalık yapıcı varyantların neden olduğu fenotipler güncel veriler ile uyumlu bulunmuştur. RASopatilerin %50’sinde PTPN11 geni patojenik varyantlarının sorumlu olduğu bilinmektedir ve kromozom analizi normal olan, klinik bulgular ile Noonan Sendromu skorlamasını karşılayan hastalarda PTPN11 dizi analizi yapılması maliyet-etkin bir yöntemdir.

Keywords

• Noonan Sendromu
• PTPN11
• Multipl Lentijinli Noonan Sendromu
• Genotip/Fenotip İlişkisi

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