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Updated: Mar 25, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Molecular Characterization of a Novel Missense Mutation (Asp538Asn) in a Chinese Patient with Factor XII Deficiency
Background:
Congenital factor XII (FXH) deficiency is an autosomal recessive disorder whose genetic basis has been described in a relatively small number of cases.
Methods:
Recently, we studied a Chinese family in which the proband had obviously prolonged activated partial thromboplastin time (APTT) associated with low functional and antigen FXII levels, 5% and 6.8%, respectively. To investigate the molecular defects in this FXII-deficient patient, we performed FXII mutation screening and invitro expression studies.
Results:
Sequence analysis of the FXII gene revealed a heterozygous G>A transition at nucleotide 8597 in exon 13, causing a novel Asp538Asn mutation in the catalytic domain.
Conclusions:
From the results above, we reasoned that this mutation must confer a cross-reacting material (CRM) negative phenotype. Additional expression studies in COS-7 cells showed that the antigen level of mutant FXII (FXII-Asp538Asn) was lower compared to the wild type in culture media, whereas the corresponding level of FXII antigen in cell lysates was equivalent roughly to that of the wild type. These findings indicated that the Asp538Asn mutation results in intracellular degradation of the mutant FXII and causes FXII deficiency.
