Korean J Lab Med.  2011 Oct;31(4):290-293. 10.3343/kjlm.2011.31.4.290.

A Novel Missense Mutation Asp506Gly in Exon 13 of the F11 Gene in an Asymptomatic Korean Woman with Mild Factor XI Deficiency

• Lee JH
• Cho HS
• Hyun MS
• Kim HY
• Kim HJ

• KMID: 1781695
• DOI: http://doi.org/10.3343/kjlm.2011.31.4.290

Abstract

Factor XI (FXI) deficiency is a rare autosomal recessive coagulation disorder most commonly found in Ashkenazi and Iraqi Jews, but it is also found in other ethnic groups. It is a trauma or surgery-related bleeding disorder, but spontaneous bleeding is rarely seen. The clinical manifestation of bleeding in FXI deficiency cases is variable and seems to poorly correlate with plasma FXI levels. The molecular pathology of FXI deficiency is mutation in the F11 gene on the chromosome band 4q35. We report a novel mutation of the F11 gene in an 18-year-old asymptomatic Korean woman with mild FXI deficiency. Pre-operative laboratory screen tests for lipoma on her back revealed slightly prolonged activated partial thromboplastin time (45.2 sec; reference range, 23.2-39.4 sec). Her FXI activity (35%) was slightly lower than the normal FXI activity (reference range, 50-150%). Direct sequence analysis of the F11 gene revealed a heterozygous A to G substitution in nucleotide 1517 (c.1517A>G) of exon 13, resulting in the substitution of aspartic acid with glycine in codon 506 (p.Asp506Gly). To the best of our knowledge, the Asp506Gly is a novel missense mutation, and this is the first genetically confirmed case of mild FXI deficiency in Korea.

Keyword

Factor XI deficiency; F11 gene; Missense mutation

MeSH Terms

Adolescent
Amino Acid Substitution
Asian Continental Ancestry Group/*genetics
Base Sequence
Chromosomes, Human, Pair 4
Exons
Factor XI Deficiency/blood/diagnosis/*genetics
Female
Heterozygote
Humans
Molecular Sequence Data
Mutation, Missense
Protein Structure, Tertiary
Republic of Korea
Sequence Analysis, DNA

Figure

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  Fig. 1 Direct sequence analysis of the F11 gene. A heterozygous missense mutation [red arrow, c.1517A>G (p.Asp506Gly)] was detected in exon 13.

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  Fig. 2 Interaction of Asp506 with Arg202 located in the A3 domain. Hydrogen-bonding interaction between these residues is indicated by a black dotted line.

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