Identification of two Novel Mutations in the Factor X Gene; A 5' Donor Splice- Site Mutation (IVS1+1G?T) and a Missense Mutation (Asp413Asn G>T) in Unrelated Palestinian Factor X Deficient Patients
Date
2015-07-20
Authors
Hisham Darwish
Journal Title
Journal ISSN
Volume Title
Publisher
OMICS Publishing Group
Abstract
Factor X deficiency is a rare autosomal disease with an estimated prevalence 1: 1,000,000. It is characterized by
a reduction in factor X, an essential component of the prothrombinase complex responsible for converting
prothrombin to thrombin. The aim of the study was to identify the molecular defects in the factor X gene in
Palestinian factor X deficient patients. Nine unrelated Palestinian patients were identified by thrombin time [PT],
activated partial thromboplastin time [APTT] and plasma factor X levels. All exons including exon/ intron border and
promoter regions were PCR amplified, purified, sequenced and compared to the normal factor X gene. A novel
splicing junction mutation IVS1+1G˃T was identified in two patients resulting in a major distortion of the protein
structure and function. A second novel missense mutation Asp413Asn G>T that apparently distorts the protein
structure and affects its catalytic activity was identified in the family of one patient. Six patients proved to be
homozygous of the previously identified c358 delG deletion mutation leading to a severely truncated protein that
seems specific to our population. A putatively mild heterozygous mutation Ser105thr G>C was detected in two
patients who suffer from the severe c358 delG deletion mutation.
Description
Keywords
Blood coagulation , Factor X gene variants , Inherited coagulation disorder; , Nucleotide deletion , Gla protein distortion and activity
Citation
Smoom R, Abushkedim I, Darwish H (2015) Identification of two Novel Mutations in the Factor X Gene; A 5' Donor Splice-Site Mutation (IVS1+1G˃T) and a Missense Mutation (Asp413Asn G>T) in Unrelated Palestinian Factor X Deficient Patients. J Blood Disord Transfus 6: 292. doi:10.4172/2155-9864.1000292