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Mutation analysis in Norwegian families with hereditary hemorrhagic telangiectasia: founder mutations in <scp>ACVRL1</scp>
- Source :
- Clinical Genetics. 89:182-186
- Publication Year :
- 2015
- Publisher :
- Wiley, 2015.
-
Abstract
- Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is an autosomal dominant inherited disease defined by the presence of epistaxis and mucocutaneous telangiectasias and arteriovenous malformations (AVMs) in internal organs. In most families (~85%), HHT is caused by mutations in the ENG (HHT1) or the ACVRL1 (HHT2) genes. Here, we report the results of genetic testing of 113 Norwegian families with suspected or definite HHT. Variants in ENG and ACVRL1 were found in 105 families (42 ENG, 63 ACVRL1), including six novel variants of uncertain pathogenic significance. Mutation types were similar to previous reports with more missense variants in ACVRL1 and more nonsense, frameshift and splice-site mutations in ENG. Thirty-two variants were novel in this study. The preponderance of ACVRL1 mutations was due to founder mutations, specifically, c.830C>A (p.Thr277Lys), which was found in 24 families from the same geographical area of Norway. We discuss the importance of founder mutations and present a thorough evaluation of missense and splice-site variants.
- Subjects :
- 0301 basic medicine
Activin Receptors, Type II
media_common.quotation_subject
DNA Mutational Analysis
Nonsense
Mucocutaneous zone
Receptors, Cell Surface
Biology
medicine.disease_cause
Frameshift mutation
Cohort Studies
03 medical and health sciences
Antigens, CD
Genetics
medicine
Humans
Missense mutation
Family
Genetics (clinical)
Genetic testing
media_common
Mutation
medicine.diagnostic_test
Norway
Endoglin
ACVRL1
Founder Effect
030104 developmental biology
Telangiectasia, Hereditary Hemorrhagic
Founder effect
Subjects
Details
- ISSN :
- 13990004 and 00099163
- Volume :
- 89
- Database :
- OpenAIRE
- Journal :
- Clinical Genetics
- Accession number :
- edsair.doi.dedup.....f866085b6ba355ff15af7b4efb6fac0f