Objective: To identify possible mutations of the SLC25A46 gene in patients with various forms of ataxia.

Background: Members of the solute carrier family 25 (SLC25) are known to transport molecules over the mitochondrial membrane. Most of the SLC25 members are located in the inner mitochondrial membrane and transport specific substrates inside and outside of the mitochondrial matrix. Several diseases are caused by mutations in the mitochondrial carrier proteins that affect either directly oxidative phosphorylation or metabolism. SLC25A46 is a novel solute carrier with higher expression levels in CNS than in periphery. Its function is totally unknown and neither functional mutations nor correlations with disease pathogenesis in animal organisms have been reported so far.

Methods: We studied 286 unrelated cases (familial and sporadic) with an ataxic phenotype, including 95 with eye problems or optic atrophy. Using direct Sanger sequencing we performed amplified each of the 8 exons of SLC25A46. Samples were sequenced using the ABI Big Dye Terminator Sequencing Kit version 1.1 on an ABI 3730xl capillary sequencer.

Results: We detected a variant in exon 1 of SLC25A46 in a patient. Insertion of a C after 166 causes frameshift and early stop in exon 1 leading to truncation of the gene products. However, this is not a pathogenic variant and does not account for the autosomal recessive mode of transmission of ataxias. No other genetic defects were identified.

Conclusions: 1. SLC25A46 genetic defects are a very rare cause of ataxia. 2. Sanger sequencing is effective and very accurate in the analysis of small genes as in this study. Looking ahead, next generation gene panels or whole exome sequencing are becoming the most efficient diagnostic tool for heterogeneous neurodegenerative disorders such as the hereditary ataxias and will soon become the initial screening method for disease genes.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/screening-for-slc25a46-mutations-in-familial-and-sporadic-ataxic-patients/