Oct 11, 2018
Sickle-Cell Disease Genetics
Sickle-Cell Disease Genetics
  Oct 11, 2018

Sickle-cell disease is caused by a gene mutation that leads to the production of Sickle haemoglobin, which affects the function of the red blood cells in the body. This mutation is inherited from the parents of an individual in an autosomal recessive pattern.

Autosomal Recessive Inheritance

The haemoglobin S gene, which is responsible for the altered haemoglobin and red blood cells, is passed on when both parents must carry the gene mutation and it affects males and females equally. This is known as an autosomal recessive pattern of inheritance.

Autosomal means that the mutation is not unique to the X or Y chromosome and can, therefore, affect males and female equally. Recessive means that the mutation much be present in both the father and the mother in order for the child to have sickle cell disease. Both parents are usually asymptomatic and may not realise that they are carriers of the mutation.

When both parents are asymptomatic genetic carriers of the disease, each child has a chance of:

  • 25% to acquire two defected genes and suffer from sickle cell disease.
  • 50% to acquire one defected gene and develop a sickle cell disease trait, asymptomatic but a genetic carrier of the disease.
  • 25% to inherit two normal genes and be unaffected by the genetic mutation and disease.

For each child that a couple has, the chance that the child will inherit the gene mutation remains the same, regardless of if previous children have been affected.

If only one parent is affected, the child may have a sickle cell trait. Children with a single gene mutation are usually healthy and do not typically experience significant side effects. However, they are a carrier of the condition and may pass the full disease on to any children, if partnered with another person with sickle cell trait.

Other Genetic Haemoglobin Diseases

The genetic mutations involved in the pathophysiology of sickle cell disease are also related to the gene mutations of other conditions involving abnormal haemoglobin, such as thalassemia, haemoglobin C, haemoglobin D and haemoglobin E.

For this reason, if one parent carries the Sickle haemoglobin gene mutation and the other carries another mutation related to haemoglobin, the risk of the child inheriting two gene mutations and suffering from the disease increases.

Genetic Testing

It is possible for an individual to determine if an individual is affected by sickle cell disease and enable earlier interventions with the help of a blood test. This test screens for the presence of defective haemoglobin characteristic of the disease.

If there is a high level of defected haemoglobin, it is likely that the individual is affected and further investigations should be made. If there are some defective cells but are not widely spread, the individual is likely to have a sickle cell trait and be less likely to experience symptoms.

The majority of newborn babies are currently screened for sickle cell disease when they have the newborn blood spot test, also known as the heel prick test. This is particularly important for high-risk populations, such as those with family origins for regions where sickle cell disease is more common.

Pregnant women are also usually offered screening for the condition, particularly in areas where it is widespread. Alternatively, they may be asked to complete a questionnaire about the family origins to determine the risk of the parents carrying sickle haemoglobin mutation.