Identification of compound heterozygous mutations p.Gly400Val and p.Arg532Ter of the F11 gene in a Chinese patient with hereditary factor XI deficiency / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the phenotype and genotype defect characteristics of a Chinese patient with hereditary factor XI deficiency.</p><p><b>METHODS</b>The activated partial thromboplastin time (APTT), prothrombin time (PT), FXI activity (FXIC) of the proband and his relatives were measured by a clotting method using automatic coagulation analyzer. FXI antigen (FXIAg) was assayed by enzyme-linked immunosorbent assay (ELISA). Fifteen exons of the F11 gene were amplified by PCR and sequenced. Pymol software was used to analyze the novel mutations.</p><p><b>RESULTS</b>The APTT of the proband was significantly prolonged (70.3 s, reference 34.5 s) with decreased FXI activity (6%, reference 50%-150%) and FXI antigen (1.9%, reference 50%-150%). The FXI activity and FXI antigen of his son was 31% and 39%, respectively. Two heterozygous F11 mutations were identified in the proband, which included a G to T substitution at nucleotide 1296 in exon 11 resulting in substitution of glycine by valine at codon 400 (p.Gly400Val) and a A to T substitution at nucleotide 1691 in exon 14 resulting in substitution of arginine (AGA) by a termination codon (TGA) at codon 532 (p.Arg532Ter). Analysis using Pymol indicated that the number of hydrogen bonds has changed, which led to a transformation of the structure of the FXI protein. The son of the proband was found to be heterozygous for the c.1296G to T (p.Gly400Val) mutation. NM_13142 c.1691A to T (p.Arg532Ter) is a novel mutation based on HGMD professional 2016.4. Based on 2015 Guidelines of ACMG, it is PVS1 (very strong pathogenicity).</p><p><b>CONCLUSION</b>The compound heterozygous mutations of F11 NM_13142 c.1296G to T (p.Gly400Val) and F11 NM_13142 c.1691A to T(p.Arg532Ter) probably underlies the FXI deficiency in the proband.</p>