In sickle cell anaemia, the mutational event responsible for the mutation for beta chain is –
**Question:** In sickle cell anaemia, the mutational event responsible for the mutation for beta chain is -
A. Val6Glu
B. Val6Glu and Glu6Val
C. Glu6Val
D. Glu6Val
**Core Concept:**
Sickle cell anaemia is a genetic disorder caused by a mutation in the HBB gene, which encodes for the beta-globin chain of hemoglobin (Hb). The disease is characterized by the production of abnormal hemoglobin molecules, which results in the sickling of red blood cells under low oxygen levels, leading to vaso-occlusion, inflammation, and tissue damage.
**Why the Correct Answer is Right:**
In the context of sickle cell anaemia, the correct answer is D: Glu6Val. This mutation involves a single nucleotide change from guanine (G) to adenine (A), which results in the substitution of glutamic acid (Glu) for valine (Val) at position 6 of the beta-globin chain. This alteration alters the stability and oxygen affinity of the Hb molecule, leading to the abnormal red blood cells' shape change and the clinical manifestations of the disease.
**Why Each Wrong Option is Incorrect:**
A. Val6Glu (Option A) and B. Val6Glu and Glu6Val (Option B) are incorrect because these options represent the opposite mutations: valine to glutamic acid (Val to Glu) and Val to Glu, respectively. These mutations would increase the stability of the Hb molecule, contradicting the pathogenesis of sickle cell anaemia.
C. Glu6Val (Option C) is also incorrect, as it only addresses one of the two common mutations (HBB:c.17G>A) responsible for sickle cell anaemia. The disease is caused by a combination of two mutations: one resulting in Glu6Val (HBB:c.17G>A) and another mutation (HBB:c.39G>A) resulting in Glu6Lys.
**Clinical Pearl:**
Glu6Val mutation is one of the two primary mutations responsible for sickle cell anaemia, which is a genetic disorder affecting the red blood cells' shape, leading to reduced oxygen carrying capacity and various clinical manifestations. Understanding these mutations is essential for diagnosing and managing patients with this disease and related disorders, such as thalassemia.