Defining the molecular pathology and consequent phenotypes in Egyptian HB patients

Ghada Y El-Kamah,Rehab M Mosaad,Mohamed B Taher,Khalda S Amr

doi:10.1186/s43141-021-00165-8

Ghada Y El-Kamah, Rehab M Mosaad + Show 2 more

Open Access

https://doi.org/10.1186/s43141-021-00165-8

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Abstract

BackgroundHemophilia B (HB) (also known as Christmas disease) is a rare X-linked recessive disorder characterized by spontaneous or prolonged hemorrhages caused by mutations in Factor 9 (F9) gene leading to deficient or defective coagulation F9. Our study aimed at identifying the causative mutations within a sample of HB Egyptian patients. The present study comprised clinical data of eleven HB patients descending from six unrelated families and a seventh family including a carrier mother with a history of deceased HB sibling. Sequencing of F9 gene was performed. ResultsThe study revealed four mutations; two missense NM_000133.3:c.676C>G, (P.Arg226Gly) and NM_000133.3:c.1305T>G, (p.Cys435Trp), and two nonsense mutations NM_000133.3:c.880C>T, (p.Arg294*) and NM_000133.3:c.1150C>T, (p.Arg384*), identified mutations spanned exons 6 and 8 of which a total of three mutations are located in hotspot exon 8 of F9 gene. ConclusionsReviewing the literature, this is the first molecular analysis of F9 gene in HB Egyptian patients. Consistent genotype/phenotypic severity correlation could be concluded, helping proper genetic counseling and prenatal decision taking.

Highlights

Hemophilia B (HB) is a rare X-linked recessive disorder characterized by spontaneous or prolonged hemorrhages caused by mutations in Factor 9 (F9) gene leading to deficient or defective coagulation F9
This study aims at the identification of pathogenic mutations verified by gene screening and describing the clinical outcomes from variants identified in a sample of Egyptian HB patients referred to the Hereditary Blood Disorders clinic, (NRC) Egypt, and develop a first step in building knowledge about the molecular basis of this disease in Egyptian patients helping to provide proper genetic counseling
Eleven HB male patients descending from six unrelated pedigrees and a seventh family including a carrier mother with a history of deceased HB patient were recruited from the Hereditary Blood Disorders clinic, National Research Centre (NRC)

Summary

Introduction

Hemophilia B (HB) ( known as Christmas disease) is a rare X-linked recessive disorder characterized by spontaneous or prolonged hemorrhages caused by mutations in Factor 9 (F9) gene leading to deficient or defective coagulation F9. Our study aimed at identifying the causative mutations within a sample of HB Egyptian patients. HB incidence is estimated as one in 30,000 live male births worldwide with rare reports of affected females [1]. Reports vary widely, and the prevalence of hemophilia B per 100,000 males in 103 countries ranged from 0.01 (Nigeria) to 8.07 (Ireland). In 2019, the World Federation of Hemophilia (WFH), in its global survey in Egyptian population (98,423,595) estimated the number of affected patients with hemophilia as 6028 [2]. Based on the plasma levels of F9, HB patients are clinically classified as severe (

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