ISSN : 2146-3123
E-ISSN : 2146-3131

Genetic Diagnosis of Hereditary Hemorrhagic Telangiectasia: Four Novel Pathogenic Variations in Turkish Patients
Mehmet Baysal1, Selma Demir2, Elif G. Ümit1, Hakan Gürkan2, Volkan Baş1, Sedanur Karaman Gülsaran1, Ufuk Demirci2, Hakkı Onur Kırkızlar1, Ahmet Muzaffer Demir1
1Department of Hematology, Trakya University School of Medicine, Edirne, Turkey
2Department of Medical Genetics, Trakya University School of Medicine, Edirne, Turkey
DOI : 10.4274/balkanmedj.galenos.2019.2019.7.2

Aims: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by telangiectasia, epistaxis and vascular malformations. Pathogenic mutations were found in ENG, AVCRL1, SMAD4 and GDF genes. In this study we tried to present our database of HHT patients regarding the phenotype-genotype relations and discuss two novel ENG gene pathogenic variations in two unrelated families.
Methods: Next Generation Sequencing analysis performed in peripheral blood of nine HHT patients in four unrelated families. All patients were diagnosed with HHT according to Curaçao criteria. Data of treatment and screenings of visceral involvement were recorded from files.
Results: We have found pathogenic variation either in ENG or ACVRL1 gene in each family. Two novel pathogenic variations in ENG gene including NM_000118.3 (ENG): c.416delC (p.P139fs*24) and NM_000118.3(ENG): c.1139dupT (p.Leu380PhefsTer16) was found in same family. NM_000020.2(ACVRL1): c.1298C>T (p.Pro433Leu) pathogenic variation in ACVRL1 gene in our first family and a novel heterozygous likely pathogenic NM_000020.2(ACVRL1): c.95T>C (p.Val32Ala) variation found in our second family. Seven of the nine patients treated with thalidomide for controlling bleeding episodes. All patients responded to thalidomide. In one patient; respond to thalidomide was lost and switched to bevacizumab.
Conclusion: In HHT certain type of mutations correlates with disease phenotypes and with next generation sequencing method, new pathogenic variations can be revealed which might help managing HHT patients.

Keywords : Hereditary hemorrhagic telangiectasia, ENG mutations, Genotype, Phenotype
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