Deep intronic variations may cause mild hemophilia A

Journal of Thrombosis and Haemostasis

Volumn 9, Issue 8, 2011, Pages 1541-1548

  Castaman, Giancarlo ^a   Giacomelli, S H ^a   Mancuso, M E ^b   D'Andrea, G ^c   Santacroce, R ^c   Sanna, S ^a   Santagostino, E ^b   Mannucci, P M ^b   Goodeve, A ^d   Rodeghiero, F ^a  

^a SAN BORTOLO HOSPITAL   (Italy)

^b UNIVERSITY OF MILAN   (Italy)

^c UNIVERSITY OF FOGGIA   (Italy)

^d UNIVERSITY OF SHEFFIELD   (United Kingdom)

Author keywords

Factor VIII; Gene mutation; Hemophilia A; Inherited bleeding disorders; MRNA

Indexed keywords

BLOOD CLOTTING FACTOR 8; DESMOPRESSIN; MESSENGER RNA;

ADULT; ARTICLE; CLINICAL ARTICLE; COMPUTER MODEL; CONTROLLED STUDY; FAMILIAL DISEASE; GENE MUTATION; HEMOPHILIA A; HETEROZYGOTE; HUMAN; INTRON; INTRON RETENTION; MALE; NUCLEOTIDE SEQUENCE; PREDICTION; PRIORITY JOURNAL; RNA TRANSCRIPTION;

ADULT; BASE SEQUENCE; BLOOD COAGULATION; CASE-CONTROL STUDIES; DEAMINO ARGININE VASOPRESSIN; DNA MUTATIONAL ANALYSIS; FACTOR VIII; FEMALE; GENETIC PREDISPOSITION TO DISEASE; HEK293 CELLS; HEMOPHILIA A; HEMOSTATICS; HEREDITY; HUMANS; INTRONS; ITALY; MALE; MIDDLE AGED; MOLECULAR SEQUENCE DATA; MUTATION; PEDIGREE; PHENOTYPE; RNA SPLICE SITES; RNA, MESSENGER; SEQUENCE ANALYSIS, RNA; SEVERITY OF ILLNESS INDEX; TRANSFECTION; YOUNG ADULT;

EID: 80051577115     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2011.04408.x     Document Type: Article

References (27)

1. Schwaab R, Oldenburg J, Schwaab U, Johnson DJ, Schmidt W, Olek K, Brackman HH, Tuddenham EG. Characterization of mutations within the factor VIII gene of 73 unrelated mild and moderate haemophiliacs. Br J Haematol 1995; 91: 458-64.
2. Bogdanova N, Markoff A, Eisert R, Wermes C, Pollman H, Todorova A, Chlystun M, Nowak-Göttl U, Horst J. Spectrum of molecular defects and mutation detection rate in patients with mild and moderate hemophilia A. Hum Mutat 2007; 28: 54-60.
3. Margaglione M, Castaman G, Morfini M, Rocino A, Santagostino E, Tagariello G, Tagliaferri AR, Zanon E, Bicocchi MP, Castaldo G, Peyvandi F, Santacroce R, Torricelli F, Grandone E, Mannucci PM; AICE-Genetics Study Group. The Italian AICE-Genetics hemophilia A database: results and correlation with clinical phenotype. Haematologica 2008; 93: 722-8.
4. Jacquemin M, De Maeyer M, D'Oiron R, Lavend'homme R, Peerlinck K, Saint-Remy J-M. Molecular mechanisms of mild and moderate hemophilia A. J Thromb Haemost 2003; 1: 456-63.
5. Castaman G, Mancuso ME, Giacomelli SH, Tosetto A, Santagostino E, Mannucci PM, Rodeghiero F. Molecular and phenotypic determinants of the response to desmopressin in adult patients with mild hemophilia A. J Thromb Haemost 2009; 7: 1824-31.
6. Tavassoli K, Eigel A, Pollmann H, Horst J. Mutational analysis of ectopic factor VIII transcripts from hemophilia A patients: identification of cryptic spice site, exon skipping and novel point mutations. Hum Genet 1997; 100: 508-11.
7. El-Maarri O, Herbiniaux U, Graw J, Schröder J, Terzic A, Watzka M, Brackmann HH, Schramm W, Hanfland P, Schwaab R, Müller CR, Oldenburg J. Analysis of mRNA in hemophilia A patients with undetectable mutations reveals normal splicing in the factor VIII gene. J Thromb Haemost 2005; 3: 332-9.
8. Rodeghiero F, Tosetto A. The epidemiology of inherited thrombophilia: the VITA Project. Vicenza thrombophilia and atherosclerosis project. Thromb Haemost 1997; 78: 636-40.
9. Castaman G, Giacomelli SH, Ghiotto R, Boseggia C, Pojani K, Bulo A, Rodeghiero F. Spectrum of mutations in Albanian patients with haemophilia A: identification of ten novel mutations in the factor VIII gene. Haemophilia 2007; 13: 311-6.
10. Dai L, Cutler JA, Savidge GF, Mitchell MJ. Characterization of a causative mutation of hemophilia A identified in the promoter region of the factor VIII gene (F8). J Thromb Haemost 2008; 6: 193-5.
11. Riccardi F, Rivolta GF, Franchini M, Pattacini C, Neri TM, Tagliaferri A. Characterization of a novel mutation in the F8 promoter region associated with mild hemophilia A and resistance to DDAVP therapy. J Thromb Haemost 2009; 7: 1234-5.
12. Castaman G, Giacomelli SH, Mancuso ME, Sanna S, Santagostino E, Rodeghiero F. F8 mRNA studied in Hemophilia A patients with different splice site mutations. Haemophilia 2010; 16: 786-90.
13. El-Maarri O, Singer H, Klein C, Watzka M, Herbiniaux U, Brackmann HH, Schröder J, Graw J, Müller CR, Schramm W, Schwaab R, Haaf T, Hanfland P, Oldenburg J. Lack of F8 mRNA: a novel mechanism leading to hemophilia A. Blood 2006; 107: 2759-65.
14. Isken O, Maquat LE. Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. Genes Dev 2007; 21: 1833-56.
15. Montefusco MC, Duga S, Asselta R, Santagostino E, Mancuso G, Malcovati M, Mannucci PM, Tenchini ML. A novel two base pair deletion in the factor V gene associated with severe factor V deficiency. Br J Haematol 2000; 111: 1240-6.
16. Soldá G, Asselta R, Ghiotto R, Tenchini ML, Castaman G, Duga S. A type II mutation(Glu117stop), induction of allele-specific mRNA degradation and factor XI deficiency. Haematologica 2005; 90: 1716-8.
17. Mikkola H, Syrjälä M, Rasi V, Vahtera E, Hämäläinen E, Peltonen L, Palotie A. Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels. Blood 1994; 84: 517-25.
18. Asselta R, Duga S, Spena S, Santagostino E, Peyvandi F, Piseddu G, Targhetta R, Malcovati M, Mannucci PM, Tenchini ML. Congenital afibrinogenemia: mutations leading to premature termination codons in fibrinogen A alpha-chain gene are not associated with the decay of the mutant mRNAs. Blood 2001; 98: 3685-92.
19. Castaman G, Platè M, Giacomelli SH, Rodeghiero F, Duga S. Alterations of mRNA processing and stability as a pathogenic mechanism in von Willebrand factor quantitative deficiencies. J Thromb Haemost 2010; 8: 2736-42.
20. Modrek B, Lee C. A genomic view of alternative splicing. Nat Genet 2002; 30: 13-9.
21. Wessagowit V, Nalla VK, Rogan PK, McGrath JA. Normal and abnormal mechanisms of gene splicing and relevance to skin disease. J Dermatol Sci 2005; 40: 73-84.
22. Gau JP, Hsu HC, Chau WK, Ho CH. A novel splicing acceptor mutation of the factor VIII gene producing skipping of exon 25. Ann Hematol 2003; 82: 175-7.
23. Bagnall RD, Waseem NH, Green PM, Colvin B, Lee C, Giannelli F. Creation of a novel donor splice site in intron 1 of the factor VIII gene leads to activation of a 191bp cryptic exon in two haemophilia patients. Br J Haematol 1999; 107: 766-71.
24. Murru S, Casula L, Pecorara M, Mori PG, Cao A, Pirastu M. Illegittimate recombination produced a duplication within the FVIII gene in a patient with mild hemophilia A. Genomics 1990; 7: 115-8.
25. Acquila M, Pasino M, Lanza T, Bottini F, Molinari AC, Bicocchi MP. Duplication of exon 13 causes one third of the cases of mild hemophilia A in northern Italy. Haematologica 2004; 88: 758-9.
26. Mironov AA, Fickett JW, Gelfand MS. Frequent alternative splicing of human genes. Genome Res 1999; 9: 1288-93.
27. Graveley BR. Alternative splicing: increasing diversity in the proteomic world. Trends Genet 2001; 17: 100-7.