Premium
Eighteen unrelated patients with factor XI deficiency, four novel mutations and a 100% detection rate by denaturing high‐performance liquid chromatography
Author(s) -
Mitchell Michael,
Harrington Purvee,
Cutler Jacqueline,
Rangarajan Savita,
Savidge Geoffrey,
Alhaq Anwar
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04302.x
Subject(s) - denaturing high performance liquid chromatography , factor xi , single strand conformation polymorphism , mutation , genetics , heterozygote advantage , compound heterozygosity , microbiology and biotechnology , biology , gene , medicine , allele , coagulation
Summary. Factor XI (FXI) deficiency is an autosomal bleeding disorder of variable severity. Inheritance is not completely recessive as heterozygotes may display a distinct, if mild, bleeding tendency. Eighteen unrelated FXI‐deficient patients were screened blind by fluorescent single‐stranded conformation polymorphism (F‐SSCP) analysis and denaturing high‐performance liquid chromatography (dHPLC). Mutations were detected in 14 of the 18 patients (∼78%) by F‐SSCP and in all 18 patients by dHPLC. Dideoxy sequencing confirmed the mutations in all 18 patients: eight of the mutations being novel (four of which were in previously reported patients). This showed dHPLC to be a highly sensitive, reliable technique for mutation screening in heterogeneous disorders.