Background: Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia disorder characterized by epistaxis, mucocutaneous telangiectasias and arteriovenous malformations in internal organs. Recurrent epistaxis is the primary complaint in 90%-96% of HHT patients and the other symptoms come with age. The aim of this study was to analyze HHT-associated gene variant spectrum in Chinese HHT patients and to assess whether genetic testing could contribute to the early diagnosis.
Methodology/principal: Thirty one HHT families including 62 individuals were recruited. Variants in the coding regions of four genes involved in HHT were amplified and analyzed using Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA).
Results: Twenty unique variants, including 8 novel variants were found in 24 of the 31 (77.4%) kindred. Diagnosis is confirmed for 7 possible individuals from 6 kindred. Thirteen ACVRL1 variants were detected from 17 isolated HHT families. Variants in ACVRL1 from 8/17 (47.1%) families were located in exon8. Seven ENG variants were found in 7 unrelated families throughout the coding region.
Conclusion: We conclude that ACVRL1 gene variant is 2.4 times more prevalent than that in ENG in Chinese individuals with HHT, and exon8 of the ACVRL1 gene may be a hotspot region. Genetic testing could contribute to early diagnosis for HHT.
Keywords: ACVRL1; ENG; epistaxis; hereditary hemorrhagic telangiectasia; variants.
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.