Review on Molecular Diagnostic Techniques in Friedreich’s Ataxia.
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Date
2013-10
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Abstract
Friedreich’s ataxia is a commonly inherited neurodegenerative disease with an autosomal
recessive pattern of inheritance, and was described by Nikolaus Friedreich first in 1863.
Friedreich’s ataxia is caused due to hyperexpansion of the intronic GAA trinucleotide
repeats or mutations in the FXN gene on chromosome 9q13. This gene codes for a
mitochondrial protein, frataxin, which is highly conserved in many species and has
functions in iron-sulfur cluster biosynthesis. Friedreich’s ataxia mainly results from a
deficiency of the frataxin protein, due to mutations in the FXN gene. Formation of sticky
DNA, formation of DNA-RNA hybrid and epigenetic changes, including methylation of DNA
and histone modifications, are the proposed mechanisms for disruption of FXN gene
expression. Most cases of Friedreich’s ataxia are homozygous and caused due to
expansion of the GAA trinucleotide repeat in the first intron of the FXN gene, however,
some cases can be heterozygous, with GAA expansion in one allele and point mutation or
deletion in the FXN gene on the other allele. Therefore, diagnosis of the disease based on
only the clinical symptoms becomes difficult. Molecular diagnosis is, therefore, important, in
order to detect GAA repeat expansions as well as mutations in the FXN gene. This review
represents an overview of the molecular diagnostic studies in Friedreich’s ataxia, including
an overview of the disease, as well as the gene and protein involved in the disease and
techniques that can be useful in diagnosis of the Friedreich’s ataxia. The described
methods include tools that are based on analysis of DNA as well as analysis of mRNA and protein levels. A brief description of mutations found in compound heterozygous
Friedreich’s ataxia patients, is also provided.
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Keywords
Friedreich’s ataxia, frataxin, GAA repeats, molecular diagnostics, triplet-repeat, primed PCR, real time PCR
Citation
Potdar Pravin D, Raghu Aarthy. Review on Molecular Diagnostic Techniques in Friedreich’s Ataxia. Annual Review & Research in Biology. 2013 Oct-Dec; 3(4): 659-677.