Restriction Endonuclease Mapping of Six Novel Deletions of the Factor VIII Gene in Hemophilia A

Overview

Journal Hum Genet

Specialty Genetics

Date 1988 Oct 1

PMID 3139545

Citations 7

Authors

H Youssoufian

C K Kasper

D G Phillips

H H Kazazian Jr

S E Antonarakis

Affiliations

Soon will be listed here.

Abstract

Hemophilia A is an X-linked disease of blood coagulation caused by deficiency of factor VIII. Using cloned cDNA, genomic and synthetic oligonucleotide factor VIII probes, we have identified six novel partial gene deletions in patients with severe hemophilia A. We have previously reported six other deletions of the factor VIII gene. The number of gross molecular defects (deletions, insertions) in the factor VIII gene in our series of 240 patients is 17 (3 insertions and 2 complicated deletions will be described elsewhere). No association was observed between the size or location of the deletions and the presence of inhibitors to factor VIII. No deletion breakpoint "hotspots" have been identified by restriction analysis. The parental origin of several of the deletions was determined.

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References

Hassan H, Leonardi A, Guerriero R, Chelucci C, Cianetti L, Ciavarella N . Hemophilia B with inhibitor: molecular analysis of the subtotal deletion of the factor IX gene. Blood. 1985; 66(3):728-30. View

Yen P, Allen E, Marsh B, Mohandas T, Wang N, Taggart R . Cloning and expression of steroid sulfatase cDNA and the frequent occurrence of deletions in STS deficiency: implications for X-Y interchange. Cell. 1987; 49(4):443-54. DOI: 10.1016/0092-8674(87)90447-8. View

Lehrman M, Goldstein J, Russell D, Brown M . Duplication of seven exons in LDL receptor gene caused by Alu-Alu recombination in a subject with familial hypercholesterolemia. Cell. 1987; 48(5):827-35. DOI: 10.1016/0092-8674(87)90079-1. View

Lazarchick J, HOYER L . Immunoradiometric measurement of the factor VIII procoagulant antigen. J Clin Invest. 1978; 62(5):1048-52. PMC: 371864. DOI: 10.1172/JCI109209. View

Koenig M, Hoffman E, Bertelson C, Monaco A, Feener C, Kunkel L . Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987; 50(3):509-17. DOI: 10.1016/0092-8674(87)90504-6. View

Nicholls R, Fischel-Ghodsian N, Higgs D . Recombination at the human alpha-globin gene cluster: sequence features and topological constraints. Cell. 1987; 49(3):369-78. DOI: 10.1016/0092-8674(87)90289-3. View

Kunkel L, Smith K, Boyer S, Borgaonkar D, Wachtel S, MILLER O . Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977; 74(3):1245-9. PMC: 430660. DOI: 10.1073/pnas.74.3.1245. View

Kazazian Jr H, Wong C, Youssoufian H, Scott A, Phillips D, Antonarakis S . Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man. Nature. 1988; 332(6160):164-6. DOI: 10.1038/332164a0. View

Harper K, Winter R, Pembrey M, Hartley D, Davies K, Tuddenham E . A clinically useful DNA probe closely linked to haemophilia A. Lancet. 1984; 2(8393):6-8. DOI: 10.1016/s0140-6736(84)91995-0. View

10.

HALDANE J . The mutation rate of the gene for haemophilia, and its segregation ratios in males and females. Ann Eugen. 2010; 13(4):262-71. DOI: 10.1111/j.1469-1809.1946.tb02367.x. View

11.

Gitschier J, Drayna D, Tuddenham E, White R, Lawn R . Genetic mapping and diagnosis of haemophilia A achieved through a BclI polymorphism in the factor VIII gene. Nature. 1985; 314(6013):738-40. DOI: 10.1038/314738a0. View

12.

Youssoufian H, Phillips D, Kazazian Jr H, Antonarakis S . MspI polymorphism in the 3' flanking region of the human factor VIII gene. Nucleic Acids Res. 1987; 15(15):6312. PMC: 306102. DOI: 10.1093/nar/15.15.6312. View

13.

Lehrman M, Russell D, Goldstein J, Brown M . Exon-Alu recombination deletes 5 kilobases from the low density lipoprotein receptor gene, producing a null phenotype in familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1986; 83(11):3679-83. PMC: 323586. DOI: 10.1073/pnas.83.11.3679. View

14.

Gitschier J, Wood W, Goralka T, Wion K, Chen E, EATON D . Characterization of the human factor VIII gene. Nature. 1984; 312(5992):326-30. DOI: 10.1038/312326a0. View

15.

Jagadeeswaran P, Tuan D, Forget B, Weissman S . A gene deletion ending at the midpoint of a repetitive DNA sequence in one form of hereditary persistence of fetal haemoglobin. Nature. 1982; 296(5856):469-70. DOI: 10.1038/296469a0. View

16.

Oberle I, Drayna D, Camerino G, White R, Mandel J . The telomeric region of the human X chromosome long arm: presence of a highly polymorphic DNA marker and analysis of recombination frequency. Proc Natl Acad Sci U S A. 1985; 82(9):2824-8. PMC: 397658. DOI: 10.1073/pnas.82.9.2824. View

17.

Myerowitz R, Hogikyan N . Different mutations in Ashkenazi Jewish and non-Jewish French Canadians with Tay-Sachs disease. Science. 1986; 232(4758):1646-8. DOI: 10.1126/science.3754980. View

18.

Antonarakis S, Waber P, Kittur S, Patel A, Kazazian Jr H, Mellis M . Hemophilia A. Detection of molecular defects and of carriers by DNA analysis. N Engl J Med. 1985; 313(14):842-8. DOI: 10.1056/NEJM198510033131402. View

19.

Itakura K, Rossi J, Wallace R . Synthesis and use of synthetic oligonucleotides. Annu Rev Biochem. 1984; 53:323-56. DOI: 10.1146/annurev.bi.53.070184.001543. View

20.

Youssoufian H, Antonarakis S, Bell W, Griffin A, Kazazian Jr H . Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides. Am J Hum Genet. 1988; 42(5):718-25. PMC: 1715175. View