Molecular Genetics


Most genetic tests have emerged from the strong research programmes on the specific diseases of interest in South Africa.

Presymptomatic testing for Huntington Disease (HD), Spinocerebellar ataxia (SCA) as well as some of the inherited forms of late onset Retinitis Pigmentosa (autosomal dominant mode of inheritance) necessitate the testing of additional family members in order to make as accurate a prediction as possible.

For these reasons it is requested that, where possible, blood be sent from an affected family member so the mutation can be confirmed in that family before undertaking predictive testing. Often, in the interest of time, blood is sent from both the affected parent or sib at the same time as the blood for the predictive test. The molecular genetic testing of the affected family member is for the at-risk individual’s predictive test and NOT for the affected patient. In addition, it must be stressed that in the case of a predictive test two DNA isolations are performed, on two separate days and two PCR reactions, again on two separate days are undertaken. This precaution is taken to avoid the possibility of misidentification of samples or something going wrong with any one test procedure. This is only done for presymptomatic testing. For the confirmation of diagnosis of an affected individual only one sample is tested.

In summary : in the case of a predictive test for an asymptomatic at-risk individual from a family with a late onset genetic condition, two DNA isolations are done ( test code : 4763) as well as two blood genotypes (PCR based tests- test code : 4765). If the predictive test is to be undertaken on a new family, where possible, one affected family member is tested (one DNA isolation and one PCR based genotype: 4763 and 4765) to confirm that the mutation is in fact detectable in that family.

In the case of Duchenne Muscular Dystrophy (DMD) (X-Linked recessive mode of inheritance) the situation is somewhat different. This condition can be as a result of a deletion or point mutation somewhere in a very large gene. Firstly, for any new DMD family the type of mutation needs to be identified in an affected boy. Once a mutation is identified, then the mother has to be investigated to see if she is a carrier. Once that is established, her sisters and daughters are all at-risk of being carriers so they might request testing. If, however, a deletion cannot be detected in the DMD gene, then linkage analysis needs to be undertaken using markers from different parts of the gene. This may become complex and requires the testing of many markers in order to get as close to the disease-causing mutation as possible. All of these tests are PCR based and could involve as few as 2 DNA extractions (code no 4763) and 6 PCR based genotype tests (code 4765) to as many as 4 DNA isolations and in excess of 10 PCR based tests for one single patient in a core family.