Genetic diagnostics of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease)
Introduction: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular disease with a worldwide prevalence of 1 : 5000 - 1 : 10 000. Diagnosis is based on clinical Curacao criteria. Approximately 85% of HHT cases have heterozygous family-specific mutations in the ENG or ACVRL1 genes. Aim: We investigated 23 Hungarian HHT families, established the genetic diagnosis, executed family-screening and confirmed founder effects. Method: Probands were identified by the stratified population screening of the primary attendance area of our institution and from individuals contacting our study group voluntarily. Diagnosis is based on the otorhinolaryngological physical examination completed with characteristic telangiectasis sites, a visceral arteriovenous malformation screening and the sequence analysis of ENG and ACVRL1 genes. The family screening consists of physical examination and genetic screening for the family-specific mutation, followed by the arteriovenous malformation screening in patients with definite/suspected HHT and/or in individuals with the mutation. Results: Sixty-three individuals with family-specific mutations were identified in 22 families, 48 of them with definite and 12 with suspected HHT. Seven ENG and ACVRL1 mutations were detected, respectively; most of these are pathogenic. Three founder mutations were observed. One proband with definite HHT had wild-type alleles in all tested HHT-specific loci. Conclusions: The significance of genetic testing is confirming or excluding HHT in young asymptomatic individuals in families with pathogenic mutations. As ENG and ACVRL1 mutations result in overlapping fenotypes, the genetic testing lacks any prognostic value. The identification of founder effects might simplify the genetic diagnosis of new HHT patients from a given region. Orv Hetil. 2019; 160(18): 710-719.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:160 |
|---|---|
| Enthalten in: |
Orvosi hetilap - 160(2019), 18 vom: 16. Mai, Seite 710-719 |
| Sprache: |
Ungarisch |
|---|
| Weiterer Titel: |
A herediter haemorrhagiás teleangiectasia (Osler–Weber–Rendu-kór) genetikai diagnosztikája |
|---|
| Beteiligte Personen: |
Major, Tamás [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 10.10.2019 Date Revised 10.10.2019 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1556/650.2019.31380 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM296504572 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM296504572 | ||
| 003 | DE-627 | ||
| 005 | 20231225090001.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||hun c | ||
| 024 | 7 | |a 10.1556/650.2019.31380 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0988.xml |
| 035 | |a (DE-627)NLM296504572 | ||
| 035 | |a (NLM)31030535 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a hun | ||
| 100 | 1 | |a Major, Tamás |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genetic diagnostics of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) |
| 246 | 3 | 3 | |a A herediter haemorrhagiás teleangiectasia (Osler–Weber–Rendu-kór) genetikai diagnosztikája |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 10.10.2019 | ||
| 500 | |a Date Revised 10.10.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Introduction: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular disease with a worldwide prevalence of 1 : 5000 - 1 : 10 000. Diagnosis is based on clinical Curacao criteria. Approximately 85% of HHT cases have heterozygous family-specific mutations in the ENG or ACVRL1 genes. Aim: We investigated 23 Hungarian HHT families, established the genetic diagnosis, executed family-screening and confirmed founder effects. Method: Probands were identified by the stratified population screening of the primary attendance area of our institution and from individuals contacting our study group voluntarily. Diagnosis is based on the otorhinolaryngological physical examination completed with characteristic telangiectasis sites, a visceral arteriovenous malformation screening and the sequence analysis of ENG and ACVRL1 genes. The family screening consists of physical examination and genetic screening for the family-specific mutation, followed by the arteriovenous malformation screening in patients with definite/suspected HHT and/or in individuals with the mutation. Results: Sixty-three individuals with family-specific mutations were identified in 22 families, 48 of them with definite and 12 with suspected HHT. Seven ENG and ACVRL1 mutations were detected, respectively; most of these are pathogenic. Three founder mutations were observed. One proband with definite HHT had wild-type alleles in all tested HHT-specific loci. Conclusions: The significance of genetic testing is confirming or excluding HHT in young asymptomatic individuals in families with pathogenic mutations. As ENG and ACVRL1 mutations result in overlapping fenotypes, the genetic testing lacks any prognostic value. The identification of founder effects might simplify the genetic diagnosis of new HHT patients from a given region. Orv Hetil. 2019; 160(18): 710-719 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a családfa | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a genetika | |
| 650 | 4 | |a hereditary hemorrhagic telangiectasia | |
| 650 | 4 | |a herediter haemorrhagiás teleangiectasia | |
| 650 | 4 | |a pedigree | |
| 650 | 4 | |a sequence analysis | |
| 650 | 4 | |a szekvenciaanalízis | |
| 650 | 7 | |a ENG protein, human |2 NLM | |
| 650 | 7 | |a Endoglin |2 NLM | |
| 650 | 7 | |a ACVRL1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.30 |2 NLM | |
| 650 | 7 | |a Activin Receptors, Type II |2 NLM | |
| 650 | 7 | |a EC 2.7.11.30 |2 NLM | |
| 700 | 1 | |a Gindele, Réka |e verfasserin |4 aut | |
| 700 | 1 | |a Szabó, Zsuzsanna |e verfasserin |4 aut | |
| 700 | 1 | |a Jóni, Natália |e verfasserin |4 aut | |
| 700 | 1 | |a Kis, Zsuzsanna |e verfasserin |4 aut | |
| 700 | 1 | |a Bora, László |e verfasserin |4 aut | |
| 700 | 1 | |a Bárdossy, Péter |e verfasserin |4 aut | |
| 700 | 1 | |a Rácz, Tamás |e verfasserin |4 aut | |
| 700 | 1 | |a Karosi, Tamás |e verfasserin |4 aut | |
| 700 | 1 | |a Bereczky, Zsuzsanna |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Orvosi hetilap |d 1949 |g 160(2019), 18 vom: 16. Mai, Seite 710-719 |w (DE-627)NLM000021601 |x 1788-6120 |7 nnns |
| 773 | 1 | 8 | |g volume:160 |g year:2019 |g number:18 |g day:16 |g month:05 |g pages:710-719 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1556/650.2019.31380 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 160 |j 2019 |e 18 |b 16 |c 05 |h 710-719 | ||