Genotype-Phenotype Heterogeneity in Haemophilia

Khan, Muhammad Tariq Masood; Taj, Abid Sohail

doi:10.5772/intechopen.81429

Cited by 5 publications

(4 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, the G allele, seen in the F9 Malmö polymorphism, c.580G > A (p.Ala 194 Thr), has a MAF of .32 38 . However, according to literature the Malmö variant has not been reported to have any association with haemophilia B 39,40 . The combined effect of this complex variant results in the amino acid change (p.Val 243 Phefs*2) within the EGF1 domain of the FIX protein.…”

Section: Discussionmentioning

confidence: 99%

Genetic variant detection in a South African haemophilia B population

Bester,

Kloppers,

van Rensburg

2024

Haemophilia

View full text Add to dashboard Cite

BackgroundHaemophilia B is characterised by a deficiency of factor IX (FIX) protein due to genetic variants in the FIX gene (F9). Genetic testing may have a vital role in effectively managing haemophilia B. However, in many developing countries, comprehensive genetic variant detection is unavailable. This study aimed to address the lack of genetic data in our country by conducting genetic variant detection on people affected by haemophilia B in our region.MethodsTwenty‐one participants were screened with a direct Sanger sequencing method to identify variants in the F9 gene. The identified variants were then compared to previously published variants and/or to a reference database.Results and DiscussionA total of ten F9 genetic changes were detected, with five of them being novel. These identified variants were distributed across different domains of the FIX protein. Only one participant had a history of inhibitor formation against FIX replacement therapy. Notably, this participant had two distinct genetic changes present adjacent to each other. Thus, we hypothesise that the presence of multiple variants within the same functional region of the gene may increase the risk for inhibitor development.ConclusionThe discovery of novel pathogenic variations in the F9 gene highlights the importance of genetic analysis in specific geographical regions. The possible link between a complex variant and inhibitor formation illustrates the potential role that genetic screening has as a pre‐treatment tool in predicting treatment reactions and outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic variant detection in a South African haemophilia B population

Bester,

Kloppers,

van Rensburg

2024

Haemophilia

View full text Add to dashboard Cite

show abstract

“…Modifier genes and environmental factors may play a role in phenotypic heterogeneity. 4,42 Determination of the parental origin of F8 pathogenic variants in pedigrees is one of the important issues in carrier detection and PND for HA. Molecular analysis of the F8 gene combined with linkage analysis using genetic markers can be useful in this regard.…”

Section: Discussionmentioning

confidence: 99%

The Spectrum of Pathogenic Variants in Iranian Families with Hemophilia A

Azadmehr¹,

Rahiminejad²,

Motlagh³

et al. 2021

Arch Iran Med

View full text Add to dashboard Cite

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.

show abstract

“…Eugenol (1-allyl-4-hydroxy-3-methoxybenzene) is the primary ingredient of Ocimum gratissimum, a phenolic compound 9 . It has a broad therapeutic activity such as analgesic 10 , anti-inflammatory 11 , anti-bacterial 12 , anti-fungal 13 , and anti-viral 14 . It is also reported that eugenol has antioxidant activity 15 , and psoriatic patients often report redox imbalance, which implies the therapeutic potential of eugenol in psoriasis.…”

Section: Introductionmentioning

confidence: 99%

Eugenol loaded lipid nanoparticles derived hydrogels ameliorate psoriasis-like skin lesions by lowering oxidative stress and modulating inflammation

Keshari,

Tharmatt,

Pillai

et al. 2024

Preprint

View full text Add to dashboard Cite

Psoriasis is a chronic T-cell-mediated autoimmune skin disorder characterized by excessive epidermal thickening, keratinocyte over-proliferation, disruption of epidermal cell differentiation, and increased blood vessel growth in the dermal layer. Despite the common use of corticosteroids in psoriasis treatment, their limited efficacy and numerous side effects pose significant challenges. This research introduces a promising alternative approach by presenting hydrogels loaded with Eugenol (EU) in combination with Carbopol 974P (EUNPGel) for potential psoriasis management. EUN-loaded lipid nanoparticles (EUNPs) exhibit superior drug loading, enhanced release kinetics, long-term stability, and the ability to scavenge reactive oxygen species (ROS). Furthermore, EUNPs have been shown to inhibit keratinocyte proliferation, induce apoptosis, and augment the uptake of IL-6-mediated inflammation in human keratinocyte cells. Application of EUNPs-loaded gels (EUNPGel) to imiquimod-induced psoriatic lesions has demonstrated effective dermal penetration, suppressing keratinocyte hyperplasia and restoring epidermal growth. This led to a remarkable reduction in the Psoriasis Area and Severity Index (PASI) score from 3. 75 to 0. 5 within five days. These findings highlight the potential of EUNPGel as an innovative nanomedicine for treating inflammation. This novel approach enhances ROS scavenging capacity, improves cellular uptake, facilitates skin penetration and retention, reduces the activity of hyperactive immune cells, and suggests potential applications for treating other immune-related disorders such as acne and atopic dermatitis.HighlightsHydrogel loaded with eugenol is an innovative alternative for psoriasis management.Superior drug loading, release kinetics, stability, and ROS scavenging capacity.Curb (human keratinocyte) HaCaT cells proliferation, induce apoptosis, lower IL-6 mediated inflammation.Effective dermal penetration and retention both in vivo and ex vivo.

show abstract

Genotype-Phenotype Heterogeneity in Haemophilia

Cited by 5 publications

References 48 publications

Genetic variant detection in a South African haemophilia B population

Genetic variant detection in a South African haemophilia B population

The Spectrum of Pathogenic Variants in Iranian Families with Hemophilia A

Eugenol loaded lipid nanoparticles derived hydrogels ameliorate psoriasis-like skin lesions by lowering oxidative stress and modulating inflammation

Contact Info

Product

Resources

About