Factor XII gene alteration in Hageman trait detected by TaqI restriction enzyme

Abstract A cDNA for coagulation factor XII has been used to investigate the presence of gene lesions and restriction fragment length polymorphisms in two brothers with Hageman trait and their family. A TaqI polymorphic fragment has been found in the two propositi and in 11 members of the paternal lineage. This polymorphism, absent in the normal population, is correlated with the reduction of factor XII activity and enables the identification of heterozygous factor XII deficiency. Factor XII gene deletion as the cause of Hageman trait in this family has been excluded. A restriction map has been constructed, and the TaqI polymorphic site has been localized within the 5′ portion of the gene. The mutation in the polymorphic site is probably the cause of the factor XII deficiency. Data suggest the presence of one factor XII gene per haploid genome.

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Factor XII gene alteration in Hageman trait detected by TaqI restriction enzyme

Blood ◽

10.1182/blood.v69.5.1421.bloodjournal6951421 ◽

1987 ◽

Vol 69 (5) ◽

pp. 1421-1424

Author(s):

F Bernardi ◽

G Marchetti ◽

P Patracchini ◽

L del Senno ◽

M Tripodi ◽

...

Keyword(s):

Gene Deletion ◽

Normal Population ◽

Coagulation Factor ◽

Polymorphic Site ◽

Restriction Map ◽

Factor Xii ◽

Polymorphic Fragment ◽

Paternal Lineage ◽

Factor Xii Deficiency ◽

Length Polymorphisms

A cDNA for coagulation factor XII has been used to investigate the presence of gene lesions and restriction fragment length polymorphisms in two brothers with Hageman trait and their family. A TaqI polymorphic fragment has been found in the two propositi and in 11 members of the paternal lineage. This polymorphism, absent in the normal population, is correlated with the reduction of factor XII activity and enables the identification of heterozygous factor XII deficiency. Factor XII gene deletion as the cause of Hageman trait in this family has been excluded. A restriction map has been constructed, and the TaqI polymorphic site has been localized within the 5′ portion of the gene. The mutation in the polymorphic site is probably the cause of the factor XII deficiency. Data suggest the presence of one factor XII gene per haploid genome.

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HAGEMAN TRAIT INVESTIGATED BY FACTOR XII cDNA PROBES

10.1055/s-0038-1643299 ◽

1987 ◽

Author(s):

S Volinia ◽

P Patracchini ◽

F Vannini ◽

L Felloni ◽

F Panicucci ◽

...

Keyword(s):

Fragment Length ◽

Gene Deletion ◽

Coagulation Factor ◽

Normal Subjects ◽

Factor Xii ◽

Chromosome 6 ◽

Paternal Lineage ◽

Length Polymorphisms ◽

Abnormal Pattern ◽

Restriction Fragment Length

The presence of gene lesions and of restriction fragment length polymorphisms (RFLPs) has been investigated by means of cDNA probes for the coagulation factor XII (FXII).A TaqI additional fragment (2.1Kb) has been found in two brothers with Hageman trait and in 11 members of their paternal lineage. Digestions with different enzymes exclude that FXII gene deletion is responsible for Hageman trait in this family. A point mutation originating an additional TaqI site is likely.The abnormal pattern (not present in 40 normal subjects) is correlated with a reduced FXII activity and identifies the heterozygous subjects in the paternal lineage. The presence of two different gene lesions causing Hageman trait in this family can be inferred.The TaqI additional site has been mapped within the 5 portion of the gene.Data suggest the presence of one FXII gene per aploid genome and disagree with previous localization of FXII gene on chromosome 6.Work supported by P.F. Ing. Gen. e Basi Mol. Mai. Ered. contratto CNR N.8400877

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A Novel Heterozygous Point Mutation Causing Coagulation Factor XII Deficiency as the Molecular Mechanism of Fatal Thrombosis Event in a Chinese Pedigree.

Blood ◽

10.1182/blood.v108.11.4080.4080 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4080-4080

Author(s):

Ying Feng ◽

Ye Xu ◽

Ying Pang ◽

Jing Dai ◽

Wei Xie ◽

...

Keyword(s):

Molecular Mechanism ◽

Coagulation Factor ◽

Laboratory Diagnosis ◽

Factor Ix ◽

The Other ◽

Heterozygous Mutation ◽

Factor Xii ◽

Phenotypic Analysis ◽

Factor Xii Deficiency ◽

Pcr Products

Abstract Objective: To study on the laboratory diagnosis and molecular mechanism of a pedigree with fatal cerebral thrombosis event caused by hereditary coagulation factor XII deficiency. Methods: Activated partial thromboplastin time (APTT), prothrombin time (PT), coagulation factor VIII activity (FVIII:C), factor IX activity (FIX:C), factor XI and factor XII activity (FXI:C and FXII:C) were determined in the propositus and the other kindred member for phenotypic analysis. All the 14 exons and their flank sequences of factor XII gene form the propositus were amplified by PCR. The purified PCR products were sequenced directly. After mutation was found, the corresponding gene fragments covering the mutated point from the other member of the kindred were amplified and sequenced. Results: The APTT of the propositus was significantly elongated (>120 seconds), while her PT was normal. Her FVIII:C,FIX:C and FXI:C were all normal. But her FXII:C was only 1 %, lower than normal. A heterozygous G3774C missense mutation in exon 4 was identified, which has led to the substitution of serine (TCT) 73 for cysteine (TGT). The sequencing results from the pedigree suggested that the other asymptomatic member of the kindred also had the same heterozygous mutation. Conclusion: The Propositus was diagnosed with inherited coagulation factor XII deficiency. The novel gene mutation found in this pedigree is the molecular mechanism leading to the fatal thrombosis events in the propositus.

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Factor XII Ofunato: Lys346Asn mutation associated with blood coagulation factor XII deficiency causes impaired secretion through a proteasome-mediated degradation

Thrombosis Research ◽

10.1016/j.thromres.2009.12.004 ◽

2010 ◽

Vol 125 (5) ◽

pp. 438-443 ◽

Cited By ~ 8

Author(s):

Keijiro Suzuki ◽

Kazunori Murai ◽

Akira Suwabe ◽

Yoji Ishida

Keyword(s):

Blood Coagulation ◽

Coagulation Factor ◽

Factor Xii ◽

Factor Xii Deficiency

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Factor XII Shizuoka, a novel mutation (Ala392Thr) identified and characterized in a patient with congenital coagulation factor XII deficiency

Thrombosis Research ◽

10.1016/j.thromres.2004.08.027 ◽

2005 ◽

Vol 115 (3) ◽

pp. 191-197 ◽

Cited By ~ 10

Author(s):

Shuji Oguchi ◽

Keiko Ishii ◽

Takanori Moriki ◽

Eiko Takeshita ◽

Mitsuru Murata ◽

...

Keyword(s):

Novel Mutation ◽

Coagulation Factor ◽

Factor Xii ◽

Factor Xii Deficiency

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Novel deleterious mutation in the F12 gene in a Korean family with severe coagulation factor XII deficiency

Blood Coagulation & Fibrinolysis ◽

10.1097/mbc.0b013e32833e429c ◽

2010 ◽

Vol 21 (7) ◽

pp. 683-686 ◽

Cited By ~ 1

Author(s):

Hee-Jung Kim ◽

Hee-Jin Kim ◽

Eui-Hoon Kwon ◽

Ki-O Lee ◽

In-Ae Park ◽

...

Keyword(s):

Deleterious Mutation ◽

Coagulation Factor ◽

Factor Xii ◽

Factor Xii Deficiency ◽

Korean Family

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Double Heterozygous Mutations (Cys247Tyr and 252delAsn) Cause Factor XII Deficiency in a Chinese Family

Hämostaseologie ◽

10.1055/a-1181-0390 ◽

2020 ◽

Vol 40 (05) ◽

pp. 650-654

Author(s):

Yu Wang ◽

Haiyue Zhang ◽

Siqi Liu ◽

Jiajia Ye

Keyword(s):

Coagulation Factor ◽

Activated Partial Thromboplastin Time ◽

Enzyme Linked Immunosorbent Assay ◽

Chinese Family ◽

Factor Xii ◽

Heterozygous Deletion ◽

Factor Xii Deficiency ◽

The World ◽

Missense Variation ◽

Exon 9

Abstract Objective To study the molecular basis of human coagulation factor XII (FXII) deficiency in a Chinese family. Methods Routine blood coagulation indexes were detected by a one-stage clotting method, whereas FXII antigen was detected by enzyme linked immunosorbent assay. DNA sequencing was applied to find mutations in the F12 gene. Bioinformatics and conservative analyses were performed to analyze possible effects of the mutation. Results The proband had significantly prolonged activated partial thromboplastin time (141.9 seconds), and her FXII clotting activity was decreased to 5%. Genetic analysis revealed that the propositus carried a heterozygous missense mutation c.797G > A in exon 8 resulting in Cys247Tyr and deletion mutation c.809_811delACA in exon 9 resulting in 252delAsn. Bioinformatics results indicated that the mutation had affected the function of the protein. Conclusion The c.797G > A heterozygous missense variation and the c.809_811delACA heterozygous deletion variation are associated with decreased FXII levels in this family, of which c.797G > A is first reported in the world.

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