Severe factor XI deficiency caused by compound heterozygosity for the type III mutation and a novel insertion in exon 9 (codons 324/325 +G)

Dossenbach‐Glaninger, Astrid; Krugluger, Walter; Schrattbauer, Karl; Eder, Sabine; Hopmeier, P.

doi:10.1046/j.1365-2141.2001.03017.x

Cited by 11 publications

(6 citation statements)

References 12 publications

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“…In the present study, we investigated the molecular basis of severe FXI deficiency in a Japanese man. To our knowledge, 34 gene mutations in patients with FXI deficiency have been reported to date [8][9][10][11][12][13]. We identified two novel mutations, a G to A transversion in exon 12 and a G insertion in exon 13, in the FXI gene.…”

Section: Discussionmentioning

confidence: 85%

“…FXI deficiency is a rare disorder most commonly found in individuals of Ashkenazi Jewish ancestry, but it has been reported sporadically in other ethnic populations [5][6][7]. So far, 34 gene mutations causing FXI deficiency have been reported [8][9][10][11][12][13], including three common mutations in Ashkenazi Jewish; a splice-junction abnormality (type I), a nonsense mutation in exon 5 (type II), and a missense mutation in exon 9 (type III). In this study, we identified two novel FXI gene mutations and compound heterozygosity for these mutations in a 25year-old Japanese male with severe FXI deficiency.…”

Section: Introductionmentioning

confidence: 99%

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Compound heterozygosity for two novel mutations in a severe factor XI deficiency

et al. 2003

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We identified two novel mutations in an asymptomatic 25-year-old Japanese patient with severe factor XI deficiency. Direct sequencing analysis of PCR products from his factor XI gene revealed a G to T transversion in exon 12, resulting in the nonsense mutation (Glu447Stop) and a G insertion in five consecutive guanine nucleotides ( 501 Trp(TGG)- 502Gly(GGG)) in exon 13 that is expected to lead to the substitution of the last 105 amino acids ( 503 Tyr-607 Val) with 32 abnormal amino acid residues ( 503 Val-534 Thr) followed by stop codon. We also demonstrated that two mutations are associated with the separate alleles in this patient, indicating compound heterozygosity for these mutations. Both mutations lead to the disruption of the catalytic domain structure of the FXI molecule and thus are responsible for his deficiency of factor XI. Am. J. Hematol. 73:279-284, 2003.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Compound heterozygosity for two novel mutations in a severe factor XI deficiency

et al. 2003

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“…Apart from the type II and type III mutations, which cause a high percentage of inherited FXI deficiency in the Jewish population (12,13), increasing numbers of causative mutations have been identified in different ethnic groups by various genetic screening methods. For the purpose of mutational analysis, the use of automated fluorescent sequencing (11,(23)(24)(25)(26), SSCP (27), dideoxyfingerprinting (22) and denaturating high-performance liquid chromatography (17) have been described. We report the application of the recently developed multitemperature single-strand conformation polymorphism analysis (MSSCP) using the DNA Pointer System.…”

Section: Discussionmentioning

confidence: 99%

Detection of single nucleotide polymorphisms in coagulation factor XI deficient patients by multitemperature single-strand conformation polymorphism analysis

Bezak¹,

Kaczanowski²,

Dossenbach‐Glaninger³

et al. 2005

J. Clin. Lab. Anal.

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Factor XI (FXI) deficiency is a rare inherited disorder which can cause bleeding complications especially in case of hemostatic challenge and/or in tissues with high fibrinolytic activity. A number of causative mutations have been described in FXI deficient individuals which have been detected by various screening methods. In this study, we present the application of the multitemperature single-strand conformation polymorphism analysis (MSSCP) on the FXI gene, a recently developed methodology for the detection of single nucleotide exchanges. We analyzed a total of 217 polymerase chain reaction (PCR) fragments from the promoter region as well as from exons 1-7 and 11-15 and compared the results to automatic fluorescent sequencing. A total of 29 PCR fragments showed single nucleotide exchanges in conventional fluorescent sequencing, representing 10 different mutations (nine missense mutations, one small deletion) and four frequent polymorphisms. With MSSCP electrophoresis at a standard temperature profile (gel temperature 35-20-10 degrees C) we were able to detect 13 of 14 (93%) different nucleotide exchanges in 25 of 29 PCR fragments (86%). Hence, the detection rate for genetic variations in the FXI gene was 86%. To evaluate the reproducibility, MSSCP was performed twice for 174 PCR fragments and the consistency between two electrophoretic runs was 99%. We conclude that the MSSCP is a sensitive, fast, and cost effective screening method for the detection of FXI gene mutations.

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“…Accordingly, most of the mutations in the factor XI gene have been described in this population [2]. A smaller number of factor XI gene mutations have also been described in other Caucasian [3], English [4], Portuguese [5], Japanese [6,7], and more recently, the French Basque [8] populations. We describe the first reported factor XI gene mutations in a Chinese family.…”

Section: Introductionmentioning

confidence: 93%

Two factor XI mutations in a Chinese family with factor XI deficiency

Cheung

Lam

et al. 2003

American J Hematol

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We describe a Chinese family with factor XI deficiency, the first reported to date. The proband had factor XI activity of 1% and was heterozygous for two nonsense mutations, an exon-8 C713 fi T mutation resulting in Gln263 fi Term, and an exon-10 C979 fi A mutation resulting in Tyr351 fi Term. Two daughters were heterozygous for the Gln263 fi Term mutation and two for the Try351 fi Term mutation. All showed a reduction of factor XI activity to about 50%. The Gln263 fi Term mutation has been described in two Japanese families, and it remains to be determined whether a common founder exists between the three kindreds. The Try351 fi Term mutation is novel. Am.

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Severe factor XI deficiency caused by compound heterozygosity for the type III mutation and a novel insertion in exon 9 (codons 324/325 +G)

Cited by 11 publications

References 12 publications

Compound heterozygosity for two novel mutations in a severe factor XI deficiency

Compound heterozygosity for two novel mutations in a severe factor XI deficiency

Detection of single nucleotide polymorphisms in coagulation factor XI deficient patients by multitemperature single-strand conformation polymorphism analysis

Two factor XI mutations in a Chinese family with factor XI deficiency

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