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Identification of three FGA mutations in two Chinese families with congenital afibrinogenaemia
Author(s) -
FANG Y.,
DAI B.T.,
WANG X.F.,
FU Q.H.,
DAI J.,
XIE F.,
CAI X.H.,
WANG H.L.,
WANG Z.Y.
Publication year - 2006
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/j.1365-2516.2006.01320.x
Subject(s) - partial thromboplastin time , exon , genetics , mutation , medicine , gene , genotype , mutation testing , prothrombin time , frameshift mutation , genetic analysis , compound heterozygosity , stop codon , microbiology and biotechnology , biology , gastroenterology , coagulation
Summary. Congenital afibrinogenaemia is a rare autosomal recessive disorder, characterized by the complete absence or extremely reduced level of fibrinogen (Fg). We attempted to analyse the phenotype and genotype in two Chinese families with congenital afibrinogenaemia. Coagulation studies including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) and Fg were performed in the patients and other family members. All the exons, exon–intron boundaries and promoter regions of three Fg genes (FGA, FGB and FGG) were screened by direct sequencing. Three patients in two families suffered from moderate to severe haemorrhage. Their APTT, PT and TT were extremely prolonged and plasma Fg levels were undetectable by Clauss method and extremely reduced by immunoassay. Genetic analysis revealed three FGA mutations in three patients including one novel mutation. In family 1, patient 1 was detected compound heterozygous mutations in FGA, g.1892–1899delAGTA/GTAA from her patriline and g.1978‐g.3215del1238 bp from her matriline. In family 2, a homozygous Gln203X in A α ‐chain was found in both patients 2 and 3 due to consanguineous marriage. All these mutations were null mutations, which could produce premature stop codons in FGA. It can be indicated that with more genetic analysis performed on afibrinogenaemia patients all over the world, there is no distinct difference in geographical distribution of Fg gene mutations. Gln203X in A α ‐chain was first reported in this study, which may help to further understand the function of A α ‐chain.