title: Severe factor XI deficiency in a Korean woman with a novel missense mutation (Val498Met) and duplication G mutation in exon 13 of the F11 gene.
abstract: Hereditary factor XI (FXI) deficiency is a rare bleeding disorder inherited in an autosomal recessive manner. The genetic background of FXI deficiency is the mutations in the F11 gene on the chromosome band 4q35. The prevalence is known to be particularly high in Ashkenazi Jews with well documented recurrent mutations; however, founder mutations in F11 have also been reported in non-Jewish patients. In this report, we describe a Korean patient with severe FXI deficiency whose causative mutations were identified by molecular genetic tests. The patient was a 33-year-old pregnant woman. Routine gynecologic workup revealed prolonged activated partial thromboplastin time. Her FXI level was severely decreased at 1% (reference range, 60-140%). Direct sequencing analysis of the F11 gene was performed to identify the causative mutations. The patient was shown to have two different mutations, c.1546 G>A (Val498Met) and c.1560dupG (Tyr503ValfsX32) in the F11 gene. Val498Met is a novel missense mutation, and the Tyr503ValfsX32 mutation was recently reported in a Japanese patient. Both mutations occurred in the exon 13 of F11 and were believed to disrupt the catalytic domain of the FXI protein, leading to severe FXI deficiency. To the best of our knowledge, this is the first genetically confirmed case of severe FXI deficiency in Korea, and more cases are needed to find any signature of founder effect in the Korean population and its potential relationship with other Asian populations.
authors.affiliation: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Seoul, Republic of Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Bang
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D020134:Catalytic Domain; D005091:Exons; D005172:Factor XI / Q000235:genetics*; D005173:Factor XI Deficiency / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007723:Korea; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics*
chemical_list: D005172:Factor XI