Eighteen unrelated patients with factor XI deficiency, four novel mutations and a 100% detection rate by denaturing high-performance liquid chromatography

被引：27

作者：

Mitchell, M ^{[1
]}

Harrington, P ^{[1
]}

Cutler, J ^{[1
]}

Rangarajan, S ^{[1
]}

Savidge, G ^{[1
]}

Alhaq, A ^{[1
]}

机构：

[1] St Thomas Hosp, Haemophilia Reference Ctr, Ctr Haemostasis & Thrombosis, London SE1 7EH, England

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2003年 / 121卷 / 03期

关键词：

factor XI deficiency; denaturing HPLC; fluorescent SSCP; mutation screening;

D O I：

10.1046/j.1365-2141.2003.04302.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (similar to78%) 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.

引用

页码：500 / 502

页数：3

共 10 条

[1] Identification of a novel mutation in a non-Jewish factor XI deficient kindred [J].

Alhaq, A ;

Mitchell, M ;

Sethi, M ;

Rahman, S ;

Flynn, G ;

Boulton, P ;

Caeno, G ;

Smith, M ;

Savidge, G .

BRITISH JOURNAL OF HAEMATOLOGY, 1999, 104 (01) :44-49

[2] ORGANIZATION OF THE GENE FOR HUMAN FACTOR-XI [J].

ASAKAI, R ;

DAVIE, EW ;

CHUNG, DW .

BIOCHEMISTRY, 1987, 26 (23) :7221-7228

[3] FACTOR-XI (PLASMA THROMBOPLASTIN ANTECEDENT) DEFICIENCY IN ASHKENAZI JEWS IS A BLEEDING DISORDER THAT CAN RESULT FROM 3 TYPES OF POINT MUTATIONS - (COAGULATION GENETIC-DEFECT POLYMERASE CHAIN-REACTION) [J].

ASAKAI, R ;

CHUNG, DW ;

RATNOFF, OD ;

DAVIE, EW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (20) :7667-7671

[4] MUTAGENIC DEAMINATION OF CYTOSINE RESIDUES IN DNA [J].

DUNCAN, BK ;

MILLER, JH .

NATURE, 1980, 287 (5782) :560-561

[5] FACTOR-XI GENE (F11) IS LOCATED ON THE DISTAL END OF THE LONG ARM OF HUMAN CHROMOSOME-4 [J].

KATO, A ;

ASAKAI, R ;

DAVIE, EW ;

AOKI, N .

CYTOGENETICS AND CELL GENETICS, 1989, 52 (1-2) :77-78

[6] The Human Gene Mutation Database [J].

Krawczak, M ;

Cooper, DN .

TRENDS IN GENETICS, 1997, 13 (03) :121-122

[7] Heterozygous factor XI deficiency associated with three novel mutations [J].

Mitchell, M ;

Cutler, J ;

Thompson, S ;

Moore, G ;

ap Rees, EJ ;

Smith, M ;

Savidge, G ;

Alhaq, A .

BRITISH JOURNAL OF HAEMATOLOGY, 1999, 107 (04) :763-765

[8]

Oefner P. J., 1995, American Journal of Human Genetics, V57, pA266

[9]

Oefner PJ, 1998, CURR PROTOCOLS HUM S, V19, P7101

[10]

*U CAL SANT CRUZ, 2002, GEN BIOINF

← 1 →