Question

A 32-year-old female patient was diagnosed with sickle cell anemia had complicated recurrent hospital admissions with vaso-occlusive crises and chest syndrome. Lab findings showed normochromic, normocytic mild to moderate anemia. Genetic investigations showed lysine was substituted for glutamine acid at position 6 on some chains and valine instead of glutamine at position 6 on other chains.  What anemia does she have and what are the two genetic (base to base changes) point mutations that cause her disease?

Answer 1

Hbs is the predominant form of haemoglobin in sickle cell patient which has a mutation in the beta chain where a glumatic acid residue is substituted for a valine ( hydrophobic) at position 6 of the beta - chain ( non conservative substitution). Homozygous expression of Hbs produces sickle cell disease (50% sickle cells) where the sickled cells are more fragile and have shorter half lives causing chronic hemolytic anemia as well as a Vasco occlusive condition (may be fatal). Also these sickle/ crescent shaped cell get trapped in small blood vessels leading to tissue damage causing various condition leading to a reduced life span.

Although the haploid human genome consists of 3 billion nucleotides, changes in even a single base can result in dramatic physiological malfunction.for eg, sickle cell anemia is a disease caused by the smallest of genetic changes.here the alterations of single nucleotide in the gene for the beta chain of the haemoglobin protein ( the oxygen carrying protein that makes blood red) is all it takes to turn a normal haemoglobin gene into sickle cell haemoglobin gene.this single nucleotide change alters only one amino acid in the protein chain but the result are devastating.