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Factor VIII gene inversions in severe hemophilia A : Results of an international consortium study

Antonarakis, S. E. ; Rossiter, J. P. ; Young, M. ; Horst, J. ; De Moerloose, P. ; Sommer, S. S. ; Ketterling, R. P. ; Kazazian, H. H. ; Négrier, C. and Vinciguerra, C. , et al. (1995) In Blood 86(6). p.2206-2212
Abstract

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells ware observed among 225 cases (≃ 1 de novo maternal origin of the inversion in 25 mothers of... (More)

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells ware observed among 225 cases (≃ 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
86
issue
6
pages
2206 - 2212
publisher
American Society of Hematology
external identifiers
  • pmid:7662970
  • scopus:0029095603
ISSN
0006-4971
DOI
10.1182/blood.v86.6.2206.bloodjournal8662206
language
English
LU publication?
yes
id
0b29fbbb-6f05-46da-bff0-96714fa5a463
date added to LUP
2020-07-31 11:34:28
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2020-10-04 08:04:33
@article{0b29fbbb-6f05-46da-bff0-96714fa5a463,
  abstract     = {<p>Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells ware observed among 225 cases (≃ 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).</p>},
  author       = {Antonarakis, S. E. and Rossiter, J. P. and Young, M. and Horst, J. and De Moerloose, P. and Sommer, S. S. and Ketterling, R. P. and Kazazian, H. H. and Négrier, C. and Vinciguerra, C. and Gitschier, J. and Goossens, M. and Girodon, E. and Ghanem, N. and Plassa, F. and Lavergne, J. M. and Vidaud, M. and Costa, J. M. and Laurian, Y. and Lin, S. W. and Lin, S. R. and Shen, M. C. and Lillicrap, D. and Taylor, S. A.M. and Windsor, S. and Valleix, S. V. and Nafa, K. and Sultan, Y. and Delpech, M. and Vnencak-Jones, C. L. and Phillips, J. A. and Ljung, R. C.R. and Koumbarelis, E. and Gialeraki, A. and Mandalaki, T. and Jenkins, P. V. and Collins, P. W. and Pasi, K. J. and Goodeve, A. and Peake, I. and Preston, F. E. and Schwartz, M. and Scheibel, E. and Ingerslev, J. and Cooper, D. N. and Millar, D. S. and Kakkar, V. V. and Giannelli, F. and Naylor, J. A. and Tizzano, E. F. and Baiget, M. and Domenech, M. and Altisent, C. and Tusell, J. and Beneyto, M. and Lorenzo, J. I. and Gaucher, C. and Mazurier, C. and Peerlinck, K. and Matthijs, G. and Cassiman, J. J. and Vermylen, J. and Mori, P. G. and Acquila, M. and Caprino, D. and Inaba, H.},
  issn         = {0006-4971},
  language     = {eng},
  month        = {09},
  number       = {6},
  pages        = {2206--2212},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Factor VIII gene inversions in severe hemophilia A : Results of an international consortium study},
  url          = {http://dx.doi.org/10.1182/blood.v86.6.2206.bloodjournal8662206},
  doi          = {10.1182/blood.v86.6.2206.bloodjournal8662206},
  volume       = {86},
  year         = {1995},
}