Molecular pathology of haemophilia A in Turkish patients: identification of 36 independent mutations

Timur, Ayse Anil; Gürgey, Aytemiz; Aktugˇlu, G.; Kavaklı, Kaan; Canatan, Duran; Olek, K.; Çagˇlayan, S. H.

doi:10.1046/j.1365-2516.2001.00548.x

Cited by 9 publications

(10 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The Arg282His missense mutation has previously been reported in several hemophilia A patients, in the HAMSTeRS hemophilia A mutation database; most of them had a severe phenotype [13,[19][20][21][22]. As shown in Fig.…”

Section: Discussionmentioning

confidence: 82%

See 1 more Smart Citation

Mutation analysis of factor VIII in Korean patients with severe hemophilia A

et al. 2010

View full text Add to dashboard Cite

Hemophilia A is an X-linked recessive disorder caused by mutations of the factor VIII gene. The mutation spectrum has been reported in various populations, but not in Koreans. Mutation analysis of the factor VIII gene was performed in 22 unrelated Korean patients with severe hemophilia A. We extracted genomic DNA from their blood, and assessed intron inversions, deletions, and point mutations by direct DNA sequencing. A multiplex ligation-dependent probe amplification gene dosage assay was also performed to identify exon deletions. Disease-causing mutations were identified in all patients, of which four cases were previously unreported. Seven intron 22 inversions, nine point mutations (6 nonsense mutations and 3 missense mutations), and four small rearrangements were identified. One multi-exon deletion and one 5'-donor splicing site mutation were also observed. Four novel mutations (one small deletion, one multiple exon deletion, one missense, and one splice site mutation) were detected, and point mutations were predominant (40.9%), followed by intron 22 inversions (31.8%). Further studies are required in order to establish a solid conclusion regarding the prevalence of various mutations in the Korean population.

show abstract

Section: Discussionmentioning

confidence: 82%

“…It has been reported that common defects found in the factor VIII gene are intron 22 inversions occurring in 40-45% of patients with severe hemophilia A [4]. Mutations other than intron 22 inversions are point mutations (85% missense and 15% nonsense), deletions, and insertions.…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis of factor VIII in Korean patients with severe hemophilia A

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Inhibitor information was available for one high-responder patient with a large deletion and two low-responder patients with a missense mutation and a small deletion [15,21]. With these additional three patients who had severe phenotype and very low levels of FVIII : C, the total number of the high-responder and lowresponder patients were 30 and six, respectively ( Table 4).…”

Section: Identification Of Mutations In Severe Hemophilia a Patients mentioning

confidence: 99%

“…F8 gene mutations have previously been identified in 97 Turkish hemophilia A patients; however, their inhibitor data were not available [15][16][17]. The present study investigates the F8 gene mutation profile of severely affected patients who developed inhibitors and estimates the risk of inhibitor development among Turkish patients with known mutations.…”

Section: Introductionmentioning

confidence: 97%

Factor 8 (F8) gene mutation profile of Turkish hemophilia A patients with inhibitors

Kavaklı²,

Uçar³

et al. 2008

Blood Coagulation &Amp; Fibrinolysis

View full text Add to dashboard Cite

Factor VIII (FVIII) replacement therapy is ineffective in hemophilia A patients who develop alloantibodies (inhibitors) against FVIII. The type of factor 8 (F8) gene mutation, genes in the major histocompatibility complex loci, and also polymorphisms in IL-10 and tumor necrosis factor-alpha are the major predisposing factors for inhibitor formation. The present study was initiated to reveal the F8 gene mutation profile of 30 severely affected high-responder patients with inhibitor levels of more than 5 Bethesda U (BU)/ml and four low-responder patients with inhibitors less than 5 BU/ml. Southern blot and PCR analysis were performed to detect intron 22 and intron 1 inversions, respectively. Point mutations were screened by DNA sequence analysis of all coding regions, intron/exon boundaries, promoter and 3' UTR regions of the F8 gene. The prevalent mutation was the intron 22 inversion among the high-responder patients followed by large deletions, small deletions, and nonsense mutations. Only one missense and one splicing error mutation was seen. Among the low-responder patients, three single nucleotide deletions and one intron 22 inversion were found. All mutation types detected were in agreement with the severe hemophilia A phenotype, most likely leading to a deficiency of and predisposition to the development of alloantibodies against FVIII. It is seen that Turkish hemophilia A patients with major molecular defects have a higher possibility of developing inhibitors.

show abstract

“…This mutation has been previously shown to affect a FVIII thrombin activation site [30,31] and has been found in association with FVIII:C ranging from <1 to 12 IU dL )1 [e.g. 27,32,33].…”

Section: Mutations In Moderate and Mild Haemophilia Amentioning

confidence: 99%

Mutation analysis in 51 patients with haemophilia A: report of 10 novel mutations and correlations between genotype and clinical phenotype

et al. 2005

View full text Add to dashboard Cite

We report the results of genetic analysis on a series of 51 patients attending this Haemophilia Comprehensive Care Centre. The most common cause of severe haemophilia A--the factor VIII intron 22 inversion was detected in eight families and the factor VIII intron 1 inversion in three families. Mutation analysis was carried out on the remaining patients by nucleotide sequencing of genomic DNA after screening with conformation-sensitive gel electrophoresis (CSGE) or denaturing high-performance liquid chromatography (dHPLC). A total of 27 different FVIII non-inversion mutations were detected. Severe haemophilia was associated with 12 null mutations (six nonsense, six frameshift) and four missense mutations. A further 11 different missense mutations were associated with moderate or mild disease. To our knowledge, six null mutations [1950del 4(tttg), 3270-75insA, 4416del 10, 6735-38delA, W1029X, Y1792X] and four missense mutations (E1682K, M1947V, P2048L, P2143L) have not been previously published. Each novel missense mutation occurred at a highly conserved residue, no other candidate mutation was detected on screening the entire coding region of the FVIII gene and they were not detected in a screen of individuals without haemophilia A. The genotype-phenotype correlations of the FVIII mutations detected will be discussed.

show abstract

Molecular pathology of haemophilia A in Turkish patients: identification of 36 independent mutations

Cited by 9 publications

References 23 publications

Mutation analysis of factor VIII in Korean patients with severe hemophilia A

Mutation analysis of factor VIII in Korean patients with severe hemophilia A

Factor 8 (F8) gene mutation profile of Turkish hemophilia A patients with inhibitors

Mutation analysis in 51 patients with haemophilia A: report of 10 novel mutations and correlations between genotype and clinical phenotype

Contact Info

Product

Resources

About