Deep intronic 'mutations' cause hemophilia A: Application of next generation sequencing in patients without detectable mutation in F8 cDNA

Journal of Thrombosis and Haemostasis

Volumn 11, Issue 9, 2013, Pages 1679-1687

  Pezeshkpoor, B ^a   Zimmer, N ^a   Marquardt, N ^a   Nanda, I ^b   Haaf, T ^b   Budde, U ^c   Oldenburg, J ^a   El Maarri, O ^a  

^a UNIVERSITY OF BONN   (Germany)

^b UNIVERSITY OF WÜRZBURG   (Germany)

^c Medilys Laborgesellschaft Hamburg   (Germany)

Author keywords

Factor VIII; hemophilia A; Introns; MRNA; Mutations

Indexed keywords

BLOOD CLOTTING FACTOR 8; COLLAGEN; COMPLEMENTARY DNA; VON WILLEBRAND FACTOR;

ADULT; ARTICLE; BINDING ASSAY; BLOOD CLOTTING; CLINICAL ARTICLE; CONTROLLED STUDY; DNA SCREENING; DNA SEQUENCE; FEMALE; GENE EXPRESSION; GENE LOCUS; GENE MUTATION; HEMOPHILIA A; HOSPITAL PATIENT; HUMAN; INTRON; MALE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN BINDING; QUALITATIVE ANALYSIS; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; SEQUENCE ANALYSIS; STOP CODON;

FACTOR VIII; HEMOPHILIA A; INTRONS; MRNA; MUTATIONS;

DNA, COMPLEMENTARY; FACTOR VIII; HEMOPHILIA A; HUMANS; INTRONS; MALE; MUTATION; REAL-TIME POLYMERASE CHAIN REACTION; RNA, MESSENGER; X CHROMOSOME INACTIVATION;

EID: 84883790923     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.12339     Document Type: Article

References (21)

1. Mazurier C, Dieval J, Jorieux S, Delobel J, Goudemand M. A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction. Blood 1990; 75: 20-6.
2. El-Maarri O, Herbiniaux U, Graw J, Schroder J, Terzic A, Watzka M, Brackmann HH, Schramm W, Hanfland P, Schwaab R, Muller 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.
3. Wang GS, Cooper TA. Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet 2007; 8: 749-61.
4. Zhang N, Kaur R, Lu X, Shen X, Li L, Legerski RJ. The Pso4 mRNA splicing and DNA repair complex interacts with WRN for processing of DNA interstrand cross-links. J Biol Chem 2005; 280: 40559-67.
5. Castaman G, Giacomelli SH, Mancuso ME, Sanna S, Santagostino E, Rodeghiero F. F8 mRNA studies in haemophilia A patients with different splice site mutations. Haemophilia 2010; 16: 786-90.
6. Castaman G, Giacomelli SH, Mancuso ME, D'Andrea G, Santacroce R, Sanna S, Santagostino E, Mannucci PM, Goodeve A, Rodeghiero F. Deep intronic variations may cause mild hemophilia A. J Thromb Haemost 2011; 9: 1541-8.
7. Santacroce R, Santoro R, Sessa F, Iannaccaro P, Sarno M, Longo V, Gallone A, Vecchione G, Muleo G, Margaglione M. Screening of mutations of hemophilia A in 40 Italian patients: a novel G-to-A mutation in intron 10 of the F8 gene as a putative cause of mild hemophilia A in southern Italy. Blood Coagul Fibrinolysis 2008; 19: 197-202.
8. Inaba H, Koyama T, Shinozawa K, Amano K, Fukutake K. Identification and characterization of an adenine to guanine transition within intron 10 of the factor VIII gene as a causative mutation in a patient with mild haemophilia A. Haemophilia 2013; 19: 100-5.
9. Hallden C, Knobe KE, Sjorin E, Nilsson D, Ljung R. Investigation of disease-associated factors in haemophilia A patients without detectable mutations. Haemophilia 2012; 18: e132-7.
10. Pezeshkpoor B, Rost S, Oldenburg J, El-Maarri O. Identification of a third rearrangement at Xq28 that causes severe hemophilia A as a result of homologous recombination between inverted repeats. J Thromb Haemost 2012; 10: 1600-8.
11. Liu Q, Nozari G, Sommer SS. Single-tube polymerase chain reaction for rapid diagnosis of the inversion hotspot of mutation in hemophilia A. Blood 1998; 92: 1458-9.
12. Bagnall RD, Waseem N, Green PM, Giannelli F. Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A. Blood 2002; 99: 168-74.
13. El-Maarri O, Singer H, Klein C, Watzka M, Herbiniaux U, Brackmann HH, Schroder J, Graw J, Muller 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. Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am J Hum Genet 1992; 51: 1229-39.
15. Oldenburg J, Schwaab R, Grimm T, Zerres K, Hakenberg P, Brackmann HH, Olek K. Direct and indirect estimation of the sex ratio of mutation frequencies in hemophilia A. Am J Hum Genet 1993; 53: 1229-38.
16. Smith NL, Chen MH, Dehghan A, Strachan DP, Basu S, Soranzo N, Hayward C, Rudan I, Sabater-Lleal M, Bis JC, de Maat MP, Rumley A, Kong X, Yang Q, Williams FM, Vitart V, Campbell H, Malarstig A, Wiggins KL, van Duijn CM, et al. Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: the CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation 2010; 121: 1382-92.
17. Klopp N, Oldenburg J, Uen C, Schneppenheim R, Graw J. 11 hemophilia A patients without mutations in the factor VIII encoding gene. Thromb Haemost 2002; 88: 357-60.
18. Chillon M, Dork T, Casals T, Gimenez J, Fonknechten N, Will K, Ramos D, Nunes V, Estivill X. A novel donor splice site in intron 11 of the CFTR gene, created by mutation 1811+1.6kbA->G, produces a new exon: high frequency in Spanish cystic fibrosis chromosomes and association with severe phenotype. Am J Hum Genet 1995; 56: 623-9.
19. Anczukow O, Buisson M, Leone M, Coutanson C, Lasset C, Calender A, Sinilnikova OM, Mazoyer S. BRCA2 deep intronic mutation causing activation of a cryptic exon: opening toward a new preventive therapeutic strategy. Clin Cancer Res 2012; 18: 4903-9.
20. Corrigan A, Arenas M, Escuredo E, Fairbanks L, Marinaki A. HPRT deficiency: identification of twenty-four novel variants including an unusual deep intronic mutation. Nucleosides, Nucleotides Nucleic Acids 2011; 30: 1260-5.
21. Xu Q, Modrek B, Lee C. Genome-wide detection of tissue-specific alternative splicing in the human transcriptome. Nucleic Acids Res 2002; 30: 3754-66.