Diagnosis and Genetic Counseling for Friedreich's Ataxia: A Time for Consideration of TP-PCR in an Indian Setup

Background And Introduction: Expansion of GAA triplet repeats in the first intron of the frataxin gene causes Friedreich's ataxia. Genetic testing in such condition is important to initiate the appropriate genetic counseling for the family members. The conventional genetic tests used in the diagnosis of Friedreich's ataxia are southern blot, short and long PCR. Recently, triplet repeat primed polymerase chain reaction (TP-PCR) methodology was described in the diagnosis of Friedreich's ataxia, especially for detection of long repeats. Accurate genetic diagnosis of Friedreich's ataxia helps in differentiating it from other ataxias and helps provide appropriate genetic counseling for such families. Extended family screening and genetic counseling can prevent birth of children with Friedreich's ataxia in these families.

Materials And Methods: TP-PCR was carried out in 37 samples obtained from Neurology clinic, Sanjay Gandhi Post Graduate Institute of Medical Sciences. The amplified products were subjected to genotyping on a ABI 310 genetic analyser. For heterozygosity, the samples were processed for short and long range PCR.

Results: A total of 37 samples of suspected cases of Friedreich ataxia were analysed. Of these, 81% samples were confirmed as Friedreich ataxia and 19% of samples were found to be negative for Friedreich's ataxia by TP-PCR. Extended family screening was done in 2 of the families. Among the 7 individuals screened, 4 were identified as carriers and genetic counseling was provided to them.

Conclusions: This is first report from India which describes the molecular diagnosis of Friedreich's ataxia by TP-PCR, its utility in extended family screening and genetic counseling. It qualifies as a highly reliable, sensitive and robust technique that can easily be set up in any laboratory.