Molecular genotyping of hemophilia A in Saudi Arabia: report of 2 novel mutations

AbstractHand surgery is a unique field that incorporates multiple specialties, aiming to provide the patient with a best possible functional and aesthetic results. Hand surgeons deal with different pathologies that require skills in several aspects of surgery. The field of hand surgery has evolved significantly over the past decades across the globe. This specialty has also been evolving in Saudi Arabia over the past 25 years. Some of the services offered to patients include specialized centers for brachial plexus, peripheral nerve, and pediatric hand surgery as well as centers for work-related hand injuries. There has also been significant contribution to the hand surgery literature from the hand surgeons working in Saudi Arabia, with hundreds of papers published in journals pertaining to hand surgery, orthopedic surgery, and plastic surgery, as well as the publication of several novel mutations causing congenital hand defects in journals concerned with genetics. The recent approval of a hand and microsurgery fellowship program in Saudi Arabia will also help boost this field in the country and the region.

Novel mutations underlying argininosuccinic aciduria in Saudi Arabia

BMC Research Notes ◽

10.1186/1756-0500-3-79 ◽

2010 ◽

Vol 3 (1) ◽

Cited By ~ 5

Author(s):

Faiqa Imtiaz ◽

Moeen Al-Sayed ◽

Danyah Trabzuni ◽

Bashair R Al-Mubarak ◽

Osama Alsmadi ◽

...

Keyword(s):

Saudi Arabia ◽

Novel Mutations ◽

Argininosuccinic Aciduria

Identification of 31 novel mutations in the F8 gene in Spanish hemophilia A patients: structural analysis of 20 missense mutations suggests new intermolecular binding sites

Blood ◽

10.1182/blood-2007-08-108068 ◽

2008 ◽

Vol 111 (7) ◽

pp. 3468-3478 ◽

Cited By ~ 10

Author(s):

Adoración Venceslá ◽

María Ángeles Corral-Rodríguez ◽

Manel Baena ◽

Mónica Cornet ◽

Montserrat Domènech ◽

...

Keyword(s):

Hemophilia A ◽

Low Density Lipoprotein ◽

Scavenger Receptor ◽

Density Lipoprotein ◽

Missense Mutations ◽

Factor X ◽

Novel Mutations ◽

Large Deletions ◽

Function Relationship ◽

The Impact

Abstract Hemophilia A (HA) is an X-linked bleeding disorder caused by a wide variety of mutations in the factor 8 (F8) gene, leading to absent or deficient factor VIII (FVIII). We analyzed the F8 gene of 267 unrelated Spanish patients with HA. After excluding patients with the common intron-1 and intron-22 inversions and large deletions, we detected 137 individuals with small mutations, 31 of which had not been reported previously. Eleven of these were nonsense, frameshift, and splicing mutations, whereas 20 were missense changes. We assessed the impact of the 20 substitutions based on currently available information about FV and FVIII structure and function relationship, including previously reported results of replacements at these and topologically equivalent positions. Although most changes are likely to cause gross structural perturbations and concomitant cofactor instability, p.Ala375Ser is predicted to affect cofactor activation. Finally, 3 further mutations (p.Pro64Arg, p.Gly494Val, and p.Asp2267Gly) appear to affect cofactor interactions with its carrier protein, von Willebrand factor, with the scavenger receptor low-density lipoprotein receptor–related protein (LRP), and/or with the substrate of the FVIIIapi•FIXa (Xase) complex, factor X. Characterization of these novel mutations is important for adequate genetic counseling in HA families, but also contributes to a better understanding of FVIII structure-function relationship.

Factor VIII (FVIII) gene mutations in 120 patients with hemophilia A: detection of 26 novel mutations and correlation with FVIII inhibitor development

Journal of Thrombosis and Haemostasis ◽

10.1111/j.1538-7836.2007.02591.x ◽

2007 ◽

Vol 5 (7) ◽

pp. 1469-1476 ◽

Cited By ~ 30

Author(s):

Y. REPESSÉ ◽

M. SLAOUI ◽

D. FERRANDIZ ◽

P. GAUTIER ◽

C. COSTA ◽

...

Keyword(s):

Factor Viii ◽

Hemophilia A ◽

Gene Mutations ◽

Novel Mutations ◽

Inhibitor Development ◽

Fviii Inhibitor

11 novel Mutations in the Factor VIII encoding Gene lead to severe or moderate Hemophilia A

32nd Hemophilia Symposium Hamburg 2001 ◽

10.1007/978-3-642-18150-4_5 ◽

2003 ◽

pp. 25-31

Author(s):

C. Uen ◽

N. Klopp ◽

J. Oldenburg ◽

H.-H. Brackmann ◽

W. Schramm ◽

...

Keyword(s):

Factor Viii ◽

Hemophilia A ◽

Novel Mutations ◽

Encoding Gene

Small FVIII gene rearrangements in 18 hemophilia A patients: Five novel mutations

American Journal of Hematology ◽

10.1002/ajh.20234 ◽

2005 ◽

Vol 78 (2) ◽

pp. 117-122 ◽

Cited By ~ 2

Author(s):

Maria Patrizia Bicocchi ◽

Mirella Pasino ◽

Tiziana Lanza ◽

Federico Bottini ◽

Angelo Claudio Molinari ◽

...

Keyword(s):

Hemophilia A ◽

Gene Rearrangements ◽

Novel Mutations

Novel Mutations Resulting in a Moderate to Severe Phenotypic Manifestation of Hemophilia A in a Female

Journal of Pediatric Hematology/Oncology ◽

10.1097/mph.0000000000000832 ◽

2017 ◽

Vol 39 (7) ◽

pp. e403-e405 ◽

Cited By ~ 1

Author(s):

Luani Barge ◽

Amy J. Holmes ◽

James Slade ◽

Nalini Pati

Keyword(s):

Hemophilia A ◽

Novel Mutations ◽

Phenotypic Manifestation

PSY58 - BUDGET IMPACT ANALYSIS OF EMICIZUMAB IN PEDIATRIC HEMOPHILIA A PATIENTS WITH INHIBITORS IN THE MINISTRY OF HEALTH (MOH), KINGDOM OF SAUDI ARABIA

Value in Health ◽

10.1016/j.jval.2018.09.2634 ◽

2018 ◽

Vol 21 ◽

pp. S445

Author(s):

A. AlJedai ◽

H. Al-Mudaiheem ◽

O. Mohamed ◽

A. Tarawah ◽

S. Al daamah ◽

...

Keyword(s):

Saudi Arabia ◽

Impact Analysis ◽

Budget Impact ◽

Hemophilia A ◽

Budget Impact Analysis ◽

Kingdom Of Saudi Arabia ◽

Ministry Of Health

Genetics and Hemostatic Potential in Persons with Mild to Moderate Hemophilia A with a Discrepancy between One-Stage and Chromogenic FVIII Assays

Thrombosis and Haemostasis ◽

10.1055/s-0040-1715443 ◽

2020 ◽

Author(s):

Annelie Strålfors ◽

Danijela Mikovic ◽

David Schmidt ◽

Liselotte Onelöv ◽

Nida Mahmoud Hourani Soutari ◽

...

Keyword(s):

Factor Viii ◽

Hemophilia A ◽

Genetic Alterations ◽

Plasma Samples ◽

Background Factor ◽

Novel Mutations ◽

Endogenous Thrombin Potential ◽

One Stage ◽

Fviii Activity ◽

A Domains

Abstract Background Factor VIII (FVIII) activity (FVIII:C) can be measured by different methods including one-stage clotting assays (OSAs) and chromogenic assays (CSAs). Discrepancy between FVIII:C assays is known and associated with genetic variations causing mild and moderate hemophilia A (HA). We aimed to study the discrepancy phenomenon and to identify associated genetic alterations. Further, we investigated if hemostatic global assays could discriminate the group with discrepant FVIII:C from them. Methods The study contained plasma samples from 45 patients with HA (PwHA) from Hemophilia Centers in Stockholm, Sweden, and Belgrade, Serbia. We measured FVIII:C with OSA and CSA, sequenced the F8 gene, and performed two global hemostatic assays; endogenous thrombin potential and overall hemostatic potential. Results Nineteen of 45 PwHA had a more than twofold higher FVIII:C using OSA compared to CSA and were considered discrepant. Thirty-four causal mutations were detected, where of five had not previously been associated with assay discrepancy. These novel mutations were p.Tyr25Cys, p.Phe698Leu, p.Met699Leu, p.Ile1698Thr, and Ala2070Val. We found no difference between discrepant and nondiscrepant cases with either of the global assays. Conclusion There was a discrepancy between FVIII:C assays in almost half of the PwHA, which for some could lead to missed HA diagnoses or misclassification of severity. Genotyping confirmed that mutations associated with FVIII:C discrepancy cluster in the A domains of F8, and five mutations not previously associated with FVIII:C discrepancy was identified. Global hemostatic assays did not contribute to distinguish assay discrepancy in PwHA.