ABSTRACT
OBJECTIVE: To analyze the phenotype and genotype in two pedigrees with hereditary coagulation factor â ª (Fâ ª) deficiency, and investigate the molecular mechanisms of Fâ ª deficiency. METHODS: Two patients with hereditary coagulation Fâ ª deficiency were admitted to Chaozhou Central Hospital in Nov 2014 and Jan 2018. The prothrombin time (PT), activated partial thromboplastin time (APTT), Fâ ª activity (Fâ ªâ¶C) and Fâ ª antigen (Fâ ªâ¶Ag) were tested for phenotypic diagnosis. All the exons and exon-intron boundaries of Fâ ª gene of proband were analyzed by PCR and sequencing. The family members were tested for the mutant site of proband. Then the mRNA of Fâ ª in the proband was analyzed with RT-PCR. RESULTS: The proband-1 was a 7-year-old boy, PT was 10.7 s and APTT was 97.4 s (reference range: 9-12.8 s; 24-40 s), Fâ ªâ¶C (0.6%) and Fâ ªâ¶Ag<1% (reference range: 65%-150%; 72.1%-122.3%). The proband-2 was a 30-year-old female, and showed the PT (11.7 s), APTT (71.3 s), Fâ ªâ¶C (0.7%) and Fâ ªâ¶Ag<1%. Fâ §â¶C, Fâ ¨â¶C and Fâ «â¶C of two proband were within the normal range. DNA sequencing showed that the proband-1 had a combined mutation of c.326-1G>A and c.1107C>A (p.Tyr351X) in exon 10. His grandmother, mother and brother had a heterozygous splicing mutation of c.326-1G>A, his grandmother and father had a homozygous mutation of c.1107C>A. FXI mRNA was undetected in the proband-1. The proband-2 had a homozygous mutation of c.841C>T (p.Gln263X) in exon 8, and this mutation was also found in her father, mother, daughter and son. CONCLUSION: The c.326-1G>A, c.1107C>A(p.Tyr351X) and c.841C>T (p.Gln263X) might be the molecular pathogenesis for two probands with hereditary coagulation factor â ª deficiency.
Subject(s)
Factor XI Deficiency , Factor XI , Pedigree , Phenotype , Adult , Child , Factor XI/genetics , Factor XI Deficiency/genetics , Female , Genotype , Heterozygote , Humans , Male , Mutation , Polymerase Chain Reaction , Sequence Analysis, DNAABSTRACT
: Coagulation factor XI (FXI) deficiency is a bleeding disorder with unpredictable severity. Patients with this condition usually suffer bleeding manifestations after trauma or surgery and are poorly correlated with plasma FXI activity (FXI:C). In the current study, we examined and identified the phenotype and genotype in four unrelated probands and their 32 relatives with hereditary FXI deficiency. The probands with severely reduced FXI:C but bleeding symptoms were only found in two probands. Mutation analysis showed that all the probands were FXI homozygous mutation or compound heterozygous mutation. Five mutations were identified including three nonsense mutations c.841C>T (p.Gln263X), c.1107C>A (p.Tyr351X) and c.1033A>T (p.Lys327X), respectively, one frameshift mutation c.1325delT (p.Leu424CysfsX8), and one splicing mutation c.326-1G>A. c.1033A>T (p. Lys327X), a novel mutation which lead to a premature stop codon at amino acid position 327, it may have an influence on protein characteristics and cause the corresponding disease.
