Jacobs Journal of Genetics

Sickle Cell Anemia: only one Single Point Mutation but Many Pathophysiological Issues

*Danilo Grünig Humberto Da Silva
Department Of Biology Hemoglobin And Hematologic, UNESP — Sao Paulo State University, Brazil

*Corresponding Author:
Danilo Grünig Humberto Da Silva
Department Of Biology Hemoglobin And Hematologic, UNESP — Sao Paulo State University, Brazil
Email:dangrunig@gmail.com

Published on: 2017-09-18

Abstract

It has been 100 years since Herrick published the first medical case report of the anemia describing abnormal shapes of red blood cells (RBCs) and gave sickle cell anemia (SCA) its name [1]. Afterwards, Vernon Ingram [2] discovered that the defect of the disease was a single aminoacid substitution in the hemoglobin (Hb) molecule (HBBglu6val), and understanding has gradually increased since then. Even with improved knowledge of the human genome, development of new genomic tools and identification of single nucleotide polymorphisms (SNPs) associated with subphenotypes of SCA by genome-wide association studies (GWAS) [3], and more than 100 different blood and urine biomarkers have been described in SCA [4]. There is still a major challenge to combine all these variables and establish potential predictors of the SCA severity [5].

Keywords

Introduction

The last 60 years have resulted in an increasingly coherent detailed molecular-level description of the SCA pathophysiology [6]. Despite our precise knowledge of the molecular defect that is associated with hemoglobin S (HbS) in RBCs [7]. Furthermore, recent progress in understanding the molecular events that control polymerization of HbS and sickling of erythrocytes [8]. Nevertheless, these mechanisms are not sufficient to explain the heterogeneous phenotype found among SCA patients, such as pain episodes, acute chest syndrome, neurological complications, leg ulcers and other symptoms. In this way, despite HbS presence is indispensable for the disease establishment, several other phenomena affected by a multitude of genes other than the one directly involved (HBB*S) play an important role [9].