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The 11 kb FGA deletion responsible for congenital afibrinogenaemia is mediated by a short direct repeat in the fibrinogen gene cluster

Honsberger, A.
Published in European Journal of Human Genetics. 1999, vol. 7, no. 8, p. 897-902
Abstract Congenital afibrinogenaemia is an autosomal recessive disorder characterised by the complete absence of detectable fibrinogen. We previously identified the first known causative mutations for this disorder in a non-consanguineous Swiss family. The four affected male individuals (two brothers and their first two cousins) were shown to have homozygous deletions of approximately 11 kb of the fibrinogen alpha chain (FGA) gene. Haplotype data suggested that the deletions occurred on three distinct ancestral chromosomes, implying that the FGA region of the fibrinogen locus is susceptible to deletion by a common mechanism, but the sequences responsible for the recombination remained to be identified. Here, we report the detailed characterisation of the deletion by nucleotide sequence analysis of all three deletion junctions and comparison with normal sequences. We found that all three deletions were identical to the base-pair and probably resulted from non-homologous (illegitimate) recombination. The centromeric and telomeric deletion junctions featured both a 7 bp direct repeat, AACTTTT, situated in FGA intron 1 and in the FGA-FGB intergenic sequence and a number of inverted repeats which could be involved in the generation of secondary structures. Analysis with closely linked flanking polymorphic markers revealed the existence of at least two haplotypes, further suggesting independent origins of the deletions in this family.
Keywords AdultAfibrinogenemia/ congenital/ geneticsBase SequenceCloning, MolecularFibrinogen/ geneticsHumansMaleMicrosatellite RepeatsMolecular Sequence DataMultigene FamilyNucleic Acid ConformationPedigreeRepetitive Sequences, Nucleic AcidSequence Deletion
PMID: 10602365
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Other version: http://www.nature.com/ejhg/journal/v7/n8/pdf/5200395a.pdf
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NEERMAN ARBEZ, Marguerite et al. The 11 kb FGA deletion responsible for congenital afibrinogenaemia is mediated by a short direct repeat in the fibrinogen gene cluster. In: European Journal of Human Genetics, 1999, vol. 7, n° 8, p. 897-902. https://archive-ouverte.unige.ch/unige:8927

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Deposited on : 2010-07-12

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