Haplotype analysis of three afibrinogenemic families with FGA 1238 bp deletion

Abstract

Congenital afibrinogenemia is characterized by the complete absence of immunoreactive fibrinogen in plasma, and its prevalence is approximately 1/1,000,000. Genetic mutations within three fibrinogen genes (FGA, FGB, and FGG coding for Aα, Bβ, and γ chain, respectively) have been associated with afibrinogenemia. FGA del c.364+86_c.510+45 (FGA Δ1238 bp) in afibrinogenemia has been reported in Japan (Mie, Okayama, Fukuoka, Gifu, and Saitama prefectures) and China (Shanghai), but regional characteristics are unknown. We identified a novel case of afibrinogenemic in a girl, the second patient in Mie, with FGA Δ1238 bp. The haplotype was identified by short tandem repeat (STR)-polymerase chain reaction (PCR) and fragment analyses using seven STR loci (D4S2962, D4S2934, D4S2999, D4S3021, intron 3 of FGA (FGA-i3), D4S2631, and D4S1629) on chromosome 4. Haplotype and clinical features were compared with those of two previously affected families (Yokkaichi and Kurashiki), and six patients were reported. Each of the three families had at least three common STR loci of D4S3021-FGA-i3-D4S2631-D4S1629 (230-del-212-146 bp) and the allele with FGA Δ1238 bp. The Mie and Okayama families may be derived from the same ancestor. Afibrinogenemic patients with FGA Δ1238 bp have been identified in Western Japan, and the continuous data accumulation by haplotype and sequence analyses should provide clues to discriminate their genetic background.