Spectrum of Novel Hereditary Hemorrhagic Telangiectasia Variants in an Austrian Patient Cohort

Martin Koenighofer; Thomas Parzefall; Alexandra Frohne; Matthew Allen; Ursula Unterberger; Franco Laccone; Christian Schoefer; Klemens Frei; Trevor Lucas

추천

검색

자료유형: 학술저널

저자정보: Martin Koenighofer Thomas Parzefall Alexandra Frohne Matthew Allen Ursula Unterberger Franco Laccone Christian Schoefer Klemens Frei Trevor Lucas

저널정보: 대한이비인후과학회 Clinical and Experimental Otorhinolaryngology Clinical and Experimental Otorhinolaryngology 제12권 제4호

발행연도: 2019.1

수록면: 405 - 411 (7page)

이용수

📌

연구주제

📖

연구배경

🔬

연구방법

🏆

연구결과

초록· 키워드

오류제보하기

Objectives. Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disorder characterized by pathogenic blood vessel development and maintenance. HHT type 1 (HHT1) and type 2 (HHT2) are caused by variants in endoglin (ENG) and activin receptor-like kinase-1 (ACVRL1), respectively. The aim of this study was to identify the spectrum of pathogenic variants in ENG and ACVRL1 in Austrian HHT families. Methods. In this prospective study, eight Austrian HHT families were screened for variants in ENG and ACVRL1 by polymerase chain reaction amplification and sequencing of DNA isolated from peripheral blood. Results. Heterozygous variants were identified in all families under study. HHT1 was caused by a novel c.816+1G>A splice donor variant, a novel c.1479C>A nonsense (p.Cys493X) variant and a published c.1306C>T nonsense (p.Gln436X) variant in ENG. Variants found in ACVRL1 were novel c.200G>C (p.Arg67Pro) and known c.772G>A (p.Gly258Ser) missense variants in highly conserved residues, a known heterozygous c.100dupT frameshift (p.Cys34Leufs*4) and the known c.1204G>A missense (p.Gly402Ser) and c.1435C>T nonsense (p.Arg479X) variants as causes of HHT2. Conclusion. Novel and published variants in ENG (37.5%) and ACVRL1 (62.5%) were exclusively identified as the cause of HHT in an Austrian patient cohort. Identification of novel causative genetics variants should facilitate the development of tailored therapeutical applications in the future treatment of autosomal dominant HHT.

참고문헌 (32)

참고문헌 신청

Schulte C / 2005 / High frequency of ENG and ALK1/ACVRL1 mutations in German HHT patients / Hum Mutat 25(6):595

McDonald J / GeneReviews: hereditary hemorrhagic telangiectasia

Westermann CJ / 2003 / The prevalence and manifestations of hereditary hemorrhagic telangiectasia in the Afro-Caribbean population of the Netherlands Antilles : a family screening / Am J Med Genet A 116(4):324~328

이승태 / 2009 / Clinical Features and Mutations in the ENG, ACVRL1, and SMAD4 genes in Korean Patients with Hereditary Hemorrhagic Telangiectasia / Journal of Korean Medical Science 24(1):69~76

Shovlin CL / 2000 / Diagnostic criteria for hereditary hemorrhagic telangiectasia(Rendu-Osler-Weber syndrome) / Am J Med Genet 91(1):66~67

함께 읽어보면 좋을 논문

논문 유사도에 따라 DBpia 가 추천하는 논문입니다. 함께 보면 좋을 연관 논문을 확인해보세요!