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Identification of nine novel mutations in type I antithrombin deficiency by heteroduplex screening
Author(s) -
Chowdhury V.,
Olds R. J.,
Lane D. A.,
Conard J.,
Pabinger I.,
Ryan K.,
Bauer K. A.,
Bhavnani M.,
Abildgaard U.,
Finazzi G.,
Castaman G.,
Mannucci P. M.,
Thein S. L.
Publication year - 1993
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1993.tb03142.x
Subject(s) - heteroduplex , point mutation , genetics , exon , biology , gene , mutation , microbiology and biotechnology , antithrombin , polymerase chain reaction , biochemistry , heparin
Summary. We have utilized DNA heteroduplex detection as a method for screening sequences of the antithrombin (AT) gene for the presence of mutations. Affected individuals from 41 kindreds with type Ia antithrombin deficiency were investigated. Heteroduplexes were detected in 12 cases; direct sequencing of the appropriate exons revealed nine cases with novel mutations, and two with previously described mutations. In addition, a new polymorphism in the 5’untranslated region was characterized. The defects included minor insertions and deletions which lead to the removal of intact codons or premature termination, and single base substitutions leading to premature termination or amino acid substitution. In all cases, the affected individuals were heterozygous for the defect and variant AT protein was not detected. In keeping with previous reports the defects associated with type Ia AT deficiency are extremely heterogeneous, the vast majority being point mutations. This study also demonstrates the efficiency of hydrolink gel electrophoresis as a method of screening for unknown mutations by heteroduplex detection.