The <scp>CDC</scp> Hemophilia B mutation project mutation list: a new online resource

Li, Tengguo; Miller, Connie H.; Payne, Amanda B.; Hooper, W. Craig

doi:10.1002/mgg3.30

Cited by 58 publications

(60 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another group of 26 mutations reportedly associate with both mild and moderate severity of the disease. 16 The high frequency of ABR, target joints, and impaired joints in patients with moderate severity is an outcome of inadequate management. Fresh frozen plasma, CS, and fresh whole blood cannot raise the FIX:C levels to the appropriate targets in settings of active bleeds.…”

Section: Discussionmentioning

confidence: 99%

“…These are mostly point mutations (73.0%), missense in the majority of the cases (74.4%). 3 Simultaneous short insertions and deletions (indels) constitute about 1.5% of the mutations, whereas gross gene deletions account for about 16.3% of the cases. Another group of mutations that occur in the promoter region of the FIX gene result in HB Leyden.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mutation Spectrum and Genotype–Phenotype Analyses in a Pakistani Cohort With Hemophilia B

Khan

Naz

Ahmed

et al. 2017

Clin Appl Thromb Hemost

View full text Add to dashboard Cite

This study aimed to (1) identify F9 genetic alterations in patients with hemophilia B (HB) of Pakistani origin and (2) determine the genotype-phenotype relationships in these patients. Diagnosed cases of HB were identified through registries at designated tertiary health-care centers across the country. Consenting patients were enrolled into the study. The factor IX (FIX) coagulation activity (FIX:C) and key clinical features were recorded. Direct sequencing of F9 was carried out in all patients. All the variants identified were analyzed for functional consequences employing in silico analysis tools. Accession numbers from National Center of Biotechnology Information ClinVar database were retrieved for the novel variants. Genotype-FIX:C relationships were determined followed by FIX:C clinical phenotype assessment. A total of 52 patients with HB from 36 unrelated families were identified, which mainly comprised patients with moderate HB (n ¼ 35; 67.3%). Among these, 35 patients from 22 unrelated families could be contacted and enrolled into the study. Missense variants were the most frequent (58.8%), followed by nonsense variants (17.6%). A missense, a short insertion, and a nonsense novel variants in exon 2, 6, and 7, respectively, were also identified. The disease manifested FIX:C heterogeneity in relation to the corresponding mutation in a significant number of cases. Clinical phenotype heterogeneity was also observed in relation to FIX:C-based severity assessment. We concluded that the registered FIX-deficient population of Pakistan mainly comprises moderate HB. F9 mutation spectrum in Pakistani patients with HB is heterogeneous. The HB population of Pakistan manifests a significant amount of genotype-FIX:C and FIX:C-clinical phenotype heterogeneities.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mutation Spectrum and Genotype–Phenotype Analyses in a Pakistani Cohort With Hemophilia B

Khan

Naz

Ahmed

et al. 2017

Clin Appl Thromb Hemost

View full text Add to dashboard Cite

show abstract

“…Severe HB patients almost have no functional FIX synthesized or secreted and have FIX activities blow 1 IU/dL, while moderate and mild HB patients only have FIX expression of function partially comprised . HB is caused by mutations of F9 gene, including single nucleotide substitutions, small insertions/deletions and large deletions . Following an X‐linked recessive mode of inheritance, HB patients are almost male and female HB patients are rare at the level of gene.…”

Section: Introductionmentioning

confidence: 99%

“…1 HB is caused by mutations of F9 gene, 2 including single nucleotide substitutions, small insertions/deletions and large deletions. [3][4][5] Following an X-linked recessive mode of inheritance, HB patients are almost male and female HB patients are rare at the level of gene.But up to 60% of female carriers experience some bleeding problems clinically. Furthermore, female carriers in HB families could pass the disorder on to their male offspring.…”

mentioning

confidence: 99%

The characteristics and spectrum of F9 mutations in Chinese sporadic haemophilia B pedigrees

Dai

et al. 2019

Haemophilia

View full text Add to dashboard Cite

Introduction Sporadic haemophilia B (HB) without obvious familial history poses challenges for genetic diagnosis and counselling. Aim To identify the F9 variants in sporadic HB patients and probe the origin of these de novo mutations. Method A total of 294 unrelated HB pedigrees sought genetic diagnosis were analysed in this single‐centre study. The F9 gene was analysed by direct sequencing, and AccuCopy technique was adopted to screen for gene copy number variations. Six short tandem repeats approximal or within F9 gene were applied for linkage analysis. Mosaicism of sequence variant was determined by ddNTP Primer Extension method. Results Sporadic HB patients constituted 36% (61/294) of cases enrolled in current study. The sporadic and familial HB patients shared similar spectrum of F9 variants, with single nucleotide substitution as predominant form of disease‐causing mutation and no mutation prone hotspot sites, including CpG dinucleotide sequences, had been identified. Majority of the mothers of sporadic HB patients were F9 mutation carriers (70%, 43/61), and most of them (95%, 41/43) had the inherited bleeding trait traced back to maternal grandfathers. Although most de novo mutations occur in germ cells, 2 maternal grandfathers, who had somatic mosaic mutations of F9, were also revealed to be the source of genetic variations identified in patients. In our cohort, FIX inhibitor incidence was 1%, developed only in patients carrying null mutations. Conclusion The diversity of F9 genetic variants and possible mosaicism of de novo mutation demand extensive study and more cautious in genetic counselling of sporadic HB.

show abstract

“…These mutations include point mutations (missense/nonsense), deletions, insertions and splicing defects. Generally, the hemophilia B cases caused by insertions ranging from a few to more than 100 base pairs are rare and account for <5 % of all hemophilia B cases [3].…”

Section: Introductionmentioning

confidence: 99%

SVA retrotransposition in exon 6 of the coagulation factor IX gene causing severe hemophilia B

et al. 2015

View full text Add to dashboard Cite

Hemophilia B is an X-linked recessive bleeding disorder caused by abnormalities of the coagulation factor IX gene (F9). Insertion mutations in F9 ranging from a few to more than 100 base pairs account for only a few percent of all hemophilia B cases. We investigated F9 to elucidate genetic abnormalities causing severe hemophilia B in a Japanese subject. We performed PCR-mediated analysis of F9 and identified a large insertion in exon 6. Next, we carried out direct sequencing of a PCR clone of the whole insert using nested deletion by exonuclease III and S1 nuclease. We identified an approximately 2.5-kb SINE-VNTR-Alu (SVA)-F element flanked by 15-bp duplications in the antisense orientation in exon 6. Additionally, we carried out exontrap analysis to assess the effect of this retrotransposition on mRNA splicing. We observed that regular splicing at exons 5 and 6 of F9 was disturbed by the SVA retrotransposition, suggesting that abnormal FIX mRNA may be reduced by nonsense-mediated mRNA decay. In conclusion, this is the first report of SVA retrotransposition causing severe hemophilia B; only five cases of LINE-1 or Alu retrotranspositions in F9 have been reported previously.

show abstract

The CDC Hemophilia B mutation project mutation list: a new online resource

Cited by 58 publications

References 18 publications

Mutation Spectrum and Genotype–Phenotype Analyses in a Pakistani Cohort With Hemophilia B

Mutation Spectrum and Genotype–Phenotype Analyses in a Pakistani Cohort With Hemophilia B

The characteristics and spectrum of F9 mutations in Chinese sporadic haemophilia B pedigrees

SVA retrotransposition in exon 6 of the coagulation factor IX gene causing severe hemophilia B

Contact Info

Product

Resources

About