Characterization of 17 novel endoglin mutations associated with hereditary hemorrhagic telangiectasiaCommunicated by Mireille Claustres.
In: Human Mutation, Jg. 21 (2003-05-01), Heft 5, S. 482-492
Online
academicJournal
Zugriff:
Hereditary hemorrhagic telangiectasia type 1 (HHT1) is a vascular dysplasia caused by mutations in the endoglin (ENG) gene and associated with epistaxis, telangiectases, and a high incidence of pulmonary arteriovenous malformations. To efficiently detect deletions and insertions, we optimized a quantitative multiplex polymerase chain reaction (QMPCR) analysis. We report 17 novel mutations, of which six were detected by QMPCR. Three deletions occurring in intronic sequences were associated with a single copy of exons 9a–14, exon 5, and exons 7–8, respectively. A transient 70kDa monomeric mutant protein resulted from the in‐frame deletion of exons 7 and 8 but no mutant protein was present in the other cases. Deletion (in exon 10) or insertion (in exon 7) of two nucleotides, as well as a 1‐bp deletion in the small exon 9a were found by QMPCR. Sequencing was required to detect single nucleotide deletions/insertions in exons 2, 5, 6, and 8. No mutant proteins were associated with these frame shift mutations. Two novel splice site mutations resulted in skipping of exons 2 and 4, respectively, while a previously reported intron 3 splice mutant was observed as a de novo mutation. We also report five novel nonsense and missense mutations, including one de novo. Review of the 80 HHT1 families reported to date indicates that 10% would not be resolved by sequencing and that an additional 25% could be revealed by QMPCR performed prior to sequencing. Thus the use of QMPCR accelerates genetic screening for HHT1 and resolves mutations affecting whole exons. Hum Mutat 21:482–492, 2003. © 2003 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]
Copyright of Human Mutation is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Titel: |
Characterization of 17 novel endoglin mutations associated with hereditary hemorrhagic telangiectasiaCommunicated by Mireille Claustres.
|
---|---|
Autor/in / Beteiligte Person: | Cymerman, Urszula ; Vera, Sonia ; Karabegovic, Amna ; Abdalla, Salma ; Letarte, Michelle |
Link: | |
Zeitschrift: | Human Mutation, Jg. 21 (2003-05-01), Heft 5, S. 482-492 |
Veröffentlichung: | 2003 |
Medientyp: | academicJournal |
ISSN: | 1059-7794 (print) |
DOI: | 10.1002/humu.10203 |
Schlagwort: |
|
Sonstiges: |
|