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Compound heterozygosity for two novel mutations in a severe factor XI deficiency
Author(s) -
Tsukahara Akiko,
Yamada Takayuki,
Takagi Akira,
Murate Takashi,
Matsushita Tadashi,
Saito Hidehiko,
Kojima Tetsuhito
Publication year - 2003
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.10378
Subject(s) - compound heterozygosity , transversion , exon , nonsense mutation , mutation , genetics , loss of heterozygosity , biology , microbiology and biotechnology , nucleotide , allele , gene , missense mutation
We identified two novel mutations in an asymptomatic 25‐year‐old Japanese patient with severe factor XI deficiency. Direct sequencing analysis of PCR products from his factor XI gene revealed a G to T transversion in exon 12, resulting in the nonsense mutation (Glu447Stop) and a G insertion in five consecutive guanine nucleotides ( 501 Trp(T GG )– 502 Gly( GGG )) in exon 13 that is expected to lead to the substitution of the last 105 amino acids ( 503 Tyr– 607 Val) with 32 abnormal amino acid residues ( 503 Val– 534 Thr) followed by stop codon. We also demonstrated that two mutations are associated with the separate alleles in this patient, indicating compound heterozygosity for these mutations. Both mutations lead to the disruption of the catalytic domain structure of the FXI molecule and thus are responsible for his deficiency of factor XI. Am. J. Hematol. 73:279–284, 2003. © 2003 Wiley‐Liss, Inc.