Academic Journal
Congenital afibrinogenemia: first identification of splicing mutations in the fibrinogen Bbeta-chain gene causing activation of cryptic splice sites
| العنوان: | Congenital afibrinogenemia: first identification of splicing mutations in the fibrinogen Bbeta-chain gene causing activation of cryptic splice sites |
|---|---|
| المؤلفون: | S. Spena, S. Duga, R. Asselta, M. Malcovati, F. Peyvandi, M.L. Tenchini |
| المساهمون: | S. Spena, S. Duga, R. Asselta, M. Malcovati, F. Peyvandi, M.L. Tenchini |
| بيانات النشر: | American Society of Hematology |
| سنة النشر: | 2002 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | A-alpha-chain, inherited afribrinogenemia, donor, truncation, thrombosi, FGA, Settore BIO/13 - Biologia Applicata, Settore BIO/11 - Biologia Molecolare |
| الوصف: | Congenital afibrinogenemia is a rare inherited coagulopathy, characterized by very low or unmeasurable plasma levels of immunoreactive fibrinogen. So far, 25 mutations have been identified in afibrinogenemia, 17 in the Aalpha, 6 in the gamma, and only 2 in the Bbeta fibrinogen-chain genes. Here, 2 afibrinogenemic probands, showing undetectable levels of functional fibrinogen, were screened for causative mutations at the genomic level. Sequence analysis of the 3 fibrinogen genes disclosed 2 novel homozygous mutations in introns 6 and 7 of the Bbeta-chain gene (IVS6 + 13C > T and IVS7 + 1G > T), representing the first Bbeta-chain gene splicing mutations described in afibrinogenemia. The IVS6 + 13C > T mutation predicts the creation of a donor splice site in intron 6, whereas the IVS7 + 1G > T mutation causes the disappearance of the invariant GT dinucleotide of intron 7 donor splice site. To analyze the effect of these mutations, expression plasmids containing Bbeta-chain minigene constructs, either wild-type or mutant, were transfected in HeLa cells. Assessed by semiquantitative analysis of reverse transcriptase-polymerase chain reaction products, the IVS7 + 1G > T mutation resulted in multiple aberrant splicings, while the IVS6 + 13C > T mutation resulted in activation of a new splice site 11 nucleotides downstream of the physiologic one. Both mutations are predicted to determine protein truncations, supporting the importance of the C-terminal domain of the Bbeta chain for fibrinogen assembly and secretion. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/12393540; info:eu-repo/semantics/altIdentifier/wos/WOS:000179759800034; volume:100; issue:13; firstpage:4478; lastpage:4484; numberofpages:7; journal:BLOOD; http://hdl.handle.net/2434/26910; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-0037114754 |
| DOI: | 10.1182/blood-2002-06-1647 |
| الاتاحة: | http://hdl.handle.net/2434/26910 https://doi.org/10.1182/blood-2002-06-1647 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.2E834339 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1182/blood-2002-06-1647 |
|---|