Prenatal diagnosis for congenital afibrinogenemia caused by a novel nonsense mutation in the FGB gene in a Palestinian family.
Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by the complete absence of detectable fibrinogen. We previously identified the first causative mutations for this disease, homozygous deletions of approximately 11 kb of the fibrinogen alpha chain gene (FGA). Subsequent analyses revealed that most afibrinogenemia alleles are truncating mutations of FGA, although mutations in all 3 fibrinogen genes, FGG, FGA and FGB have been identified. In this study, we performed the first prenatal diagnosis for afibrinogenemia. The causative mutation in a Palestinian family was a novel nonsense mutation in the FGB gene, Trp467Stop (W467X). Expression of the Trp467Stop mutant FGB cDNA in combination with wild-type FGA and FGG cDNAs showed that fibrinogen molecules containing the mutant beta chain are not secreted into the media. The fetus was found to be heterozygous for the Trp467Stop mutation by direct sequencing and by linkage analysis, a result that was confirmed in the newborn by intermediate fibrinogen levels.
Neerman-Arbez
Marguerite
M
Division of Medical Genetics, University Medical School and University Hospital, Geneva, Switzerland. marguerite.arbez@medecine.unige.ch
Vu
Dung
D
Abu-Libdeh
Bassam
B
Bouchardy
Isabelle
I
Morris
Michael A
MA
D000022:Abortion, Spontaneous; D000347:Afibrinogenemia / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics; D000595:Amino Acid Sequence; D000649:Amniocentesis; D018912:Arabs / Q000235:genetics*; D003062:Codon / Q000235:genetics; D018389:Codon, Nonsense; D003241:Consanguinity; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics; D005340:Fibrinogen / Q000737:chemistry / Q000235:genetics*; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006474:Hemorrhagic Disorders / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree
C115499:BBeta fibrinogen; D003062:Codon; D018389:Codon, Nonsense; D018076:DNA, Complementary; D005340:Fibrinogen