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Independent occurrence of the novel Arg 2163 to His mutation in the factor VIII gene in three unrelated families with haemophilia A with different phenotypes
Author(s) -
Theophilus Bimal D. M.,
Enayat Mohammad S.,
Higuchi Miyoko,
Kazazian Haig H.,
Antonarakis Stylianos E.,
Hill Frank G. H.
Publication year - 1998
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1998)11:4<334::aid-humu21>3.0.co;2-x
Subject(s) - biology , genetics , phenotype , haemophilia a , mutation , gene , haemophilia
Using chemical mismatch analysis or denaturing gradient gel electrophoresis followed by nucleotide sequencing, we have identified the same G6545A mutation leading to an Arg 2163 His substitution in the factor VIII gene of three haemophiliacs from unrelated families. One of the affected individuals has severe haemophilia, while the other two are moderately severe. While we cannot exclude the possibility that these differences in phenotype arise from differences in VIII:C assay methods, other studies have also identified different clinical phenotypes in individuals with the same mutations, and suggested that they may arise from extragenic factors that affect or modify gene expression or protein function. The G6545A mutation occurs at a CG dinucleotide which is a known mutation hotspot, and which may explain the independent occurrence in unrelated families. Hum Mutat 11:334, 1998. © 1998 Wiley‐Liss, Inc.