Recurrence of the 'deep-intronic' FGG IVS6-320A>T mutation causing quantitative fibrinogen deficiency in the Italian population of Veneto.
Quantitative fibrinogen deficiency is a rare bleeding disorder characterized by abnormally low levels of fibrinogen in plasma, generally due to mutations in one of the three fibrinogen genes: FGA, FGB, and FGG, coding for A alpha, B beta, and gamma chain, respectively. Although the partial defect (hypofibrinogenemia) is due to mutations occurring in the heterozygous state, homozygosity or compound heterozygosity for the same genetic defects give rise to the more severe afibrinogenemia. Mutations responsible for these conditions are scattered throughout the three fibrinogen genes, with only few sites representing relative mutational hot spots. In this study, we report the identification of the FGG IVS6-320A>T mutation in an Italian hypofibrinogenemic patient from Veneto (a region of North-Eastern Italy). This 'deep-intronic' mutation, which would go unnoticed by using conventional mutational screening strategies was previously reported in an afibrinogenemic family from Vicenza (a province of Veneto). The geographic clustering of patients carrying the FGG IVS6-320A>T mutation and the results of haplotype analysis suggest the existence of a common founder. This information will be useful to direct future genetic screenings in patients coming from the same geographic area.
Platè
Manuela
M
Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy.
Duga
Stefano
S
Castaman
Giancarlo
G
Rodeghiero
Francesco
F
Asselta
Rosanna
R
D000328:Adult; D000347:Afibrinogenemia / Q000453:epidemiology / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics; D015241:Fibrinogens, Abnormal / Q000032:analysis / Q000235:genetics*; D018703:Founder Effect; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D008297:Male; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D018389:Codon, Nonsense; D015241:Fibrinogens, Abnormal