Part of the reason that South African CF patients tend to die prematurely is because they are often diagnosed late. Children born with CF tend to have three main symptoms. Their sweat contains elevated levels of chloride and they have many chest infections. They also fail to thrive (which means they are short for their age and underweight).
Diagnosing CF is not straightforward. First, it was assumed that CF could only affect Caucasian patients, which is not the case. However, this idea still lingers, increasing the likelihood that CF patients of other ethnicities may be underdiagnosed. Second, there are other illnesses with symptoms similar to CF that occur more frequently in South Africa, such as tuberculosis (TB). This means that a CF patient may be mistaken for having TB, for example. Third, the ‘gold standard’ CF test – known as the sweat test – may miss some CF patients.
A genetic test for CF would be a reliable way to identify all true CF patients but this has its own challenges. CF is caused by mutations in the CFTR gene. The current genetic test for CF patients in South Africa was developed based on data obtained from French patients. When this test was performed locally on 171 suspected CF patients, 30% of the genes assessed returned a result of unknown mutation. This could mean either that they did not have CF or that they carried mutations that are not typically seen in France.
In order to test the latter hypothesis, Professor Michael Pepper and Dr Cheryl Stewart of the Institute for Cellular and Molecular Medicine (ICCM) have sequenced the CFTR gene of 50 suspected CF patients on whom an incomplete genetic diagnosis had been made. They found 21 mutations that are not on the current (French) test, four of which had never been identified before anywhere in the world. This supports the fact that CF mutations are population specific. Initially, 59% of the genes in the cohort of 50 patients had a test result of unknown mutation, which they were able to reduce to 26% on the basis of the new mutations they had discovered. They anticipate that the data could be used to refine the current genetic test used to screen South African patients. If a South African test was used to identify patients earlier, it would help CF patients live longer and healthier lives.
Dr Cheryl Stewart
