Identification Of A Novel Deletion Mutation Of F13A Gene In A Pedigree With Factor XIII Deficiency

OBJECTIVE: To explore F13 gene mutation in a pedigree with hereditary coagulation factor XIII (FXIII) deficiency.METHODS: 1) Coagulation screening tests the hematologic tests included activated partial thromboplastin time (APTT), prothrombin time (PT), and clot solubility. Laboratory diagnosis of FXIII deficiency was made where the clot solubility test result with 5M urea.2) the peripheral blood mononuclear cells (PBMCs) were separated from whole blood using lymphoprep (Nycorma Birmingham UK), according to the manufacturer's instructions. 3) PCR of genomic DNA, sequence analysis of PCR products. The coding regions and the intron exon boundaries of the A-subunit gene were screened for nucleotide sequence changes by polymerase chain reaction (PCR) amplification.The PCR fragments were sequenced after solid phase purification by the Sanger dideoxy-chain termination methodRESULTS: The assays of PT,aPTT,bleeding time,fibrinogen level,platelet counts were normal and the clot solubility test was positive in the proband. The homozygous deletion mutation (1319-1351del33) in exon 10 of F13A gene was identified in the proband. Family studies showed that the mutation was inherited from the parents who were the correspondingly were heterozygous for this same delation 406-416mutation. This results in an in-frame deletion of 33 amino acids. Which encode part of the coar domain of FXIII A-subunit intron sequence becomes incorporated into the mRNA,which would result in a premature stop codon.CONCLUSION: the patient was diagnosed as hereditary FXIII deficiency;The homozygous 127067del33 mutation of F13 gene is responsible for the disorder of the pedigree.