Spectrum of <i>F8</i> gene mutations in haemophilia A patients from Slovenia

Debeljak, Maruša; Kitanovski, Lidija; Bakija, Alenka Trampuš; Dolničar, Majda Benedik

doi:10.1111/hae.12003

Cited by 2 publications

(2 citation statements)

References 19 publications

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“…One is the F8 gene coding for the coagulation factor VIII, a known susceptibility gene for venous thrombosis ( 38 ). The reported uAUG creating variant is the NM_000132.4:c.-5A>G variant that creates an overlapping upORF of 63 nucleotides ( 20 ). Very interestingly, this variant is simultaneously predicted to modify a TAA stop codon into a TGA, in frame with two different non-canonical TIS (CTG) generating fully upstream upORFs of 39 and 123 nucleotides.…”

Section: Resultsmentioning

confidence: 99%

Common and Rare 5′UTR Variants Altering Upstream Open Reading Frames in Cardiovascular Genomics

Soukarieh

Meguerditchian

Proust

et al. 2022

Front. Cardiovasc. Med.

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High-throughput sequencing (HTS) technologies are revolutionizing the research and molecular diagnosis landscape by allowing the exploration of millions of nucleotide sequences at an unprecedented scale. These technologies are of particular interest in the identification of genetic variations contributing to the risk of rare (Mendelian) and common (multifactorial) human diseases. So far, they have led to numerous successes in identifying rare disease-causing mutations in coding regions, but few in non-coding regions that include introns, untranslated (UTR), and intergenic regions. One class of neglected non-coding variations is that of 5′UTR variants that alter upstream open reading frames (upORFs) of the coding sequence (CDS) of a natural protein coding transcript. Following a brief summary of the molecular bases of the origin and functions of upORFs, we will first review known 5′UTR variations altering upORFs and causing rare cardiovascular disorders (CVDs). We will then investigate whether upORF-affecting single nucleotide polymorphisms could be good candidates for explaining association signals detected in the context of genome-wide association studies for common complex CVDs.

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Section: Resultsmentioning

confidence: 99%

Common and Rare 5′UTR Variants Altering Upstream Open Reading Frames in Cardiovascular Genomics

Soukarieh

Meguerditchian

Proust

et al. 2022

Front. Cardiovasc. Med.

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“…No variant has been reported so far in codon 1787, but amino acid substitution, from histidine to residues with different properties (leucine/aspartic/tyrosine) at position 2174 has been reported previously. [31][32][33][34] The variant c.5359G > A results in a substitution of an acidic residue (Glu) for a basic residue (Lys) but c.6521A > G replaces one amino acid with another amino acid in the same amino acid group. Therefore, although variant c.6521A > G has already been reported as a pathogenic variant in the f8-db.eahad.org database, it can be suggested that based on two moderate and two supporting evidence of pathogenicity (PM1 PM2 PP2 PP3), the c.5359G > A (p.Glu1787Lys) variant is the cause of the disease.…”

Section: Discussionmentioning

confidence: 99%

The Spectrum of Pathogenic Variants in Iranian Families with Hemophilia A

Azadmehr¹,

Rahiminejad²,

Motlagh³

et al. 2021

Arch Iran Med

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Background: Hemophilia A (HA) is an X-linked recessive bleeding disorder with a high rate of genetic heterogeneity. The present study was conducted on a large cohort of Iranian HA patients and data obtained from databases. Methods: A total of 622 Iranian HA patients from 329 unrelated families who had been referred to a medical genetics laboratory in Tehran from 2005 to 2019, were enrolled in this retrospective, observational study. Genetic screening of pathogenic variants of the F8 gene was performed using inverse shifting PCR, direct sequencing, and multiplex ligation-dependent amplification (MLPA). Point mutation frequencies in different exons were analyzed for our samples as well as 6031 HA patients whose data were recorded in a database. Results: A total of 144 different pathogenic or likely pathogenic variants including 29 novel variants were identified. A strategy to decrease costs of genetic testing of HA was suggested based on this finding. Conclusion: This study provides comprehensive information on F8 pathogenic/likely pathogenic variants in Iranian HA patients which improves the spectrum of causative mutations and can be helpful to clinicians and medical geneticists in counseling and molecular diagnosis of HA.

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Spectrum of F8 gene mutations in haemophilia A patients from Slovenia

Cited by 2 publications

References 19 publications

Common and Rare 5′UTR Variants Altering Upstream Open Reading Frames in Cardiovascular Genomics

Common and Rare 5′UTR Variants Altering Upstream Open Reading Frames in Cardiovascular Genomics

The Spectrum of Pathogenic Variants in Iranian Families with Hemophilia A

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