F8 gene dosage defects in atypical patients with severe haemophilia A
Por:
Vencesla, A, Baena, M, Garrido, RP, Nunez, R, Velasco, F, Rosell, J, Villar, A, Jimenez-Yuste, V, Baiget, M, Tizzano, EF
Publicada:
1 sep 2012
Resumen:
. We performed molecular analysis of the factor 8 gene (F8) in 272 unrelated Spanish patients with haemophilia A (HA) and detected a mutation by routine analysis in 267 of them (98.1%). No mutation was detected in the remaining five patients despite clinical and laboratory confirmation of HA. The aim is to describe the molecular alterations in F8 discovered by gene dosage methodologies in three of these patients. For methodology, F8 sequencing, intragenic marker analysis, multiplex ligation-dependent probe amplification and quantitative real time-PCR were followed. One patient had Klinefelter syndrome (47,XXY) and a large deletion spanning exons 112 masked by the other F8 allele; the second patient showed a large duplication spanning exons 210 and the third patient revealed a non-contiguous double duplication of exons 14 and 2325. The remaining two patients had mild HA and dosage results were normal. The application of gene dosage methods is useful to define haemophilic patients in whom mutations are not detected using other routine methods. Nevertheless, in a small percentage of patients (<1%), no molecular pathology can be identified after testing several genetic methodologies.
Filiaciones:
Vencesla, A:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain
CIBERER U705, Barcelona 08025, Spain
Baena, M:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain
CIBERER U705, Barcelona 08025, Spain
Garrido, RP:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain
CIBERER U705, Barcelona 08025, Spain
Hosp Virgen del Rocio, Unidad Hemofilia, Seville, Spain
Nunez, R:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain
CIBERER U705, Barcelona 08025, Spain
Hosp Virgen del Rocio, Unidad Hemofilia, Seville, Spain
Velasco, F:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain
CIBERER U705, Barcelona 08025, Spain
Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Spain
Rosell, J:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain
CIBERER U705, Barcelona 08025, Spain
Hosp Son Espases, Serv Genet, Palma De Mallorca, Spain
Villar, A:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain
CIBERER U705, Barcelona 08025, Spain
Hosp La Paz, Unidad Hemofilia, Madrid, Spain
Jimenez-Yuste, V:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain
CIBERER U705, Barcelona 08025, Spain
Hosp La Paz, Unidad Hemofilia, Madrid, Spain
Baiget, M:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain
CIBERER U705, Barcelona 08025, Spain
Tizzano, EF:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08025, Spain
CIBERER U705, Barcelona 08025, Spain
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