A complete deficiency of coagulation factor XIII A‐subunit due to a novel compound heterozygote of Ser 413 Leu missense and an nt 389 (ins G) frameshift mutation

Niiya, Toshiyuki; Osawa, Haruhiko; Bando, Shiro; Oto, Yoshiko; Tokuda, Kazuhiro; Takeda, Namiko; Sumioka, Maki; Murase, Mitsuharu; Kida, Kaichi; Makino, Hideichi

doi:10.1046/j.1365-2141.1999.01764.x

Cited by 16 publications

(8 citation statements)

References 12 publications

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“…A previously reported missense mutation in exon 10, c.1241C>T, p.Ser413Leu, was identified in family E (one homozygote, two heterozygotes). Consistent with previous reports [22,23] the homozygote had no detectable FXIII-A antigen, indicating again rapid degradation of the faulty protein.…”

Section: Sequence Analysissupporting

confidence: 92%

“…Two of them, c.1040C>A, p.Ala346Asp and c.1126T>C, p.Trp375Arg, were novel and they were both found only in single homozygous cases. The third missense mutation, c.1241C>T, p.Ser413Leu, has already been reported in one patient from India (homozygous) [22] and one from Japan [23] (compound heterozygous). Patients homozygous for any of these three missense mutations had no detectable FXIII-A antigen and FXIII activity.…”

Section: Discussionmentioning

confidence: 99%

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Congenital factor XIII deficiency in Pakistan: characterization of seven families and identification of four novel mutations

et al. 2013

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Deficiency of coagulation factor XIII (FXIII) belongs to the rare bleeding disorders and its incidence is higher in populations with consanguineous marriages. The aims of this study were to characterize patients and relatives from seven families with suspected FXIII deficiency from Pakistan and to identify the underlying mutations. As a first indicator of FXIII deficiency, a 5M urea clot solubility test was used. Plasma FXIII A- and B-subunit antigen levels were determined by ELISA. FXIII activity was measured with an incorporation assay. Sequencing of all exons and intron/exon boundaries of F13A was performed, and a novel splice site defect was confirmed by RT-PCR analysis. Genetic analysis revealed six different mutations in the F13A gene. Two splice site mutations were detected, a novel c.1460+1G>A mutation in the first nucleotide of intron 11 and a previously reported c.2045G>A mutation in the last nucleotide of exon 14. Neither of them was expressed at protein level. A novel nonsense mutation in exon 4, c.567T>A, p.Cys188X, was identified, leading in homozygous form to severe FXIII deficiency. Two novel missense mutations were found in exons 8 and 9, c.1040C>A, p.Ala346Asp and c.1126T>C, p.Trp375Arg, and a previously reported missense mutation in exon 10, c.1241C>T, p.Ser413Leu. All patients homozygous for these missense mutations presented with severe FXIII deficiency. We have analysed a cohort of 27 individuals and reported four novel mutations leading to congenital FXIII deficiency.

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Section: Sequence Analysissupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Congenital factor XIII deficiency in Pakistan: characterization of seven families and identification of four novel mutations

et al. 2013

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“…Most cases of FXIII deficiency are the result of mutations in the gene encoding FXIII-A. Forty-eight mutations involving the FXIII-A gene have been characterized so far: 26 missense and 3 nonsense, 11 small insertion/deletions, one large deletion and seven nucleotide substitutions in splice site junctions [see Anwar and Milozewski, 1999;Niiya et al, 1999;Anwar et al, 2000;Anwar et al, 2001;Gomez et al, 2001;Birben et al, 2002]. In this manuscript we report 6 mutations causing FXIII deficiency in 10 unrelated homozygous patients from Iran, a population with a high rate of consanguinity that has been poorly studied so far.…”

Section: Introductionmentioning

confidence: 99%

Phenotype-genotype characterization of 10 families with severe a subunit factor XIII deficiency

et al. 2003

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Factor XIII (FXIII) deficiency is a very rare severe autosomal bleeding disorder with a frequency of 1:2,000,000 in the general population and only a few patients have been genetically characterized so far. We report a phenotype-genotype characterization of 10 unrelated Iranian patients. Two FXIII (transglutaminase) activity assays showed no FXIII activity, except a conserved residual activity in patients receiving prophylactic substitution treatment. FXIII antigen concentrations measured by two immunoassays were comparable. Genotype characterization identified four novel mutations (2 missense and 2 small deletions) and two previously reported missense mutations in the FXIII A subunit gene (F13A). Molecular modeling was carried out to reveal the structural consequences of the missense mutations, that caused the replacement of an arginine residue involved in the formation of structurally important extensive hydrogen-bonded network. The replacements [c.320G>A (p.Arg77His) in the beta-sandwich, c.868C>T (p.Arg260Cys), c.869G>A (p.Arg260His) and c.1236G>T (p.Arg382Ser) in the core domain] resulted in the loss or impairment of such H-bonded network. Energy decomposition analysis demonstrated that this situation leads to the instability and perhaps to the incorrect folding of the A subunit, that would explain the development of severe FXIII deficiency.

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“…The sequence was initially determined using a reverse primer designed in exon 1 (mPDE5-R), and forward and reverse primers were then subsequently designed based on the determined sequence ( Table 2). The DNA sequencing reaction was performed using previously described methods [23,24].…”

Section: Isolation Of the 5p £Anking Sequence Of The Mouse Pde3b Genementioning

confidence: 99%

Activation of mouse phosphodiesterase 3B gene promoter by adipocyte differentiation in 3T3‐L1 cells

et al. 2001

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Activation of phosphodiesterase (PDE) 3B reduces free fatty acid output from adipocytes. Induction of PDE3B gene expression by adipocyte differentiation could improve insulin resistance. To examine whether the PDE3B promoter is activated by this differentiation, the 5P P flanking sequence of the mouse PDE3B gene was isolated. The transcription initiation site was determined to be located 195 bp upstream of the translation start site. No putative binding site for peroxisome proliferatoractivated receptor Q Q was found within 2 kb upstream of the transcription initiation site. This region had promoter activity, which was further activated on adipocyte differentiation in 3T3-L1 cells. ß

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A complete deficiency of coagulation factor XIII A‐subunit due to a novel compound heterozygote of Ser 413 Leu missense and an nt 389 (ins G) frameshift mutation

Cited by 16 publications

References 12 publications

Congenital factor XIII deficiency in Pakistan: characterization of seven families and identification of four novel mutations

Congenital factor XIII deficiency in Pakistan: characterization of seven families and identification of four novel mutations

Phenotype-genotype characterization of 10 families with severe a subunit factor XIII deficiency

Activation of mouse phosphodiesterase 3B gene promoter by adipocyte differentiation in 3T3‐L1 cells

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