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Thromb Haemost 2000; 84(01): 49-53
DOI: 10.1055/s-0037-1613966
Commentary
Schattauer GmbH

A Case of Congenital Afibrinogenemia: Fibrinogen Hakata, a Novel Nonsense Mutation of the Fibrinogen γ-Chain Gene

Hiroko Iida
1   From the Department of Clinical Chemistry and Laboratory Medicine, Fukuoka, Japan
,
Eiichi Ishii
3   Department of Pediatrics, Hamanomachi Hospital, Fukuoka, Japan
,
Mutsuko Nakahara
1   From the Department of Clinical Chemistry and Laboratory Medicine, Fukuoka, Japan
,
Michiyo Urata
1   From the Department of Clinical Chemistry and Laboratory Medicine, Fukuoka, Japan
,
Machiko Wakiyama
1   From the Department of Clinical Chemistry and Laboratory Medicine, Fukuoka, Japan
,
Masako Kurihara
1   From the Department of Clinical Chemistry and Laboratory Medicine, Fukuoka, Japan
,
Kumiko Watanabe
1   From the Department of Clinical Chemistry and Laboratory Medicine, Fukuoka, Japan
,
Takeshi Kai
3   Department of Pediatrics, Hamanomachi Hospital, Fukuoka, Japan
,
Kenji Ihara
2   Department of Pediatrics, Kyushu University Hospital, Fukuoka, Japan
,
Sachiko Kinoshita
1   From the Department of Clinical Chemistry and Laboratory Medicine, Fukuoka, Japan
,
Naotaka Hamasaki
1   From the Department of Clinical Chemistry and Laboratory Medicine, Fukuoka, Japan
› Author AffiliationsWe wish to thank Professor Sheshadri Narayaman, New York Medical College (USA), for critically reading this manuscript. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (to NH), and by a P&P Grant from Kyushu University (to NH).
Further Information

Publication History

Received 30 November 1999

Accepted after resubmission 15 February 2000

Publication Date:
10 December 2017 (online)

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Summary

Congenital afibrinogenemia due to a novel homozygous nonsense mutation of the fibrinogen γ-chain gene, fibrinogen Hakata, was found in an 18-year-old Japanese girl who had received supplemental fibrinogen therapy since she was 4 months old. The plasma fibrinogen concentrations of the proband were measured as less than 10 mg/dl by a functional method and less than 17 mg/dl by an immunological method. Fibrinogen concentrations of her family were in the range of 94-164 mg/dl. The proband and her family had no other clinical symptoms.

Genomic DNA of the proband and her family was isolated from leukocytes, and all exons of fibrinogen subunits and their intron/exon boundaries were analyzed. A genetic mutation, a guanine-to-thymine (G-to-T) transversion at the nucleotide position of 5860, was identified on exon 7 of the γ-chain gene. This mutation changed the codon for the 231st residue of the γ chain from GAG (Glu) to TAG (stop). No other mutation was observed. Aα, Bβ and γ chains were observed in plasma of the heterozygous family members. However, only a trace amount of Aα chain and no γ chain was detected in the plasma of the proband.

Keywords

Afibrinogenemia - γ chain of fibrinogen - nonsense mutation - gene analysis
 

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