The mitochondrial solute carrier SLC25A5 at Xq24 is a novel candidate gene for non-syndromic intellectual disability.

Human genetics 2013 Oct

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Loss-of-function mutations in several different neuronal pathways have been related to intellectual disability (ID). Such mutations often are found on the X chromosome in males since they result in functional null alleles. So far, microdeletions at Xq24 reported in males always have been associated with a syndromic form of ID due to the loss of UBE2A. Here, we report on overlapping microdeletions at Xq24 that do not include UBE2A or affect its expression, in patients with non-syndromic ID plus some additional features from three unrelated families. The smallest region of overlap, confirmed by junction sequencing, harbors two members of the mitochondrial solute carrier family 25, SLC25A5 and SLC25A43. However, identification of an intragenic microdeletion including SLC25A43 but not SLC25A5 in a healthy boy excluded a role for SLC25A43 in cognition. Therefore, our findings point to SLC25A5 as a novel gene for non-syndromic ID. This highly conserved gene is expressed ubiquitously with high levels in cortex and hippocampus, and a presumed role in mitochondrial exchange of ADP/ATP. Our data indicate that SLC25A5 is involved in memory formation or establishment, which could add mitochondrial processes to the wide array of pathways that regulate normal cognitive functions.

Citation

Joke Vandewalle, Marijke Bauters, Hilde Van Esch, Stefanie Belet, Jelle Verbeeck, Nathalie Fieremans, Maureen Holvoet, Jodie Vento, Ana Spreiz, Dieter Kotzot, Edda Haberlandt, Jill Rosenfeld, Joris Andrieux, Bruno Delobel, Marie-Bertille Dehouck, Koen Devriendt, Jean-Pierre Fryns, Peter Marynen, Amy Goldstein, Guy Froyen. The mitochondrial solute carrier SLC25A5 at Xq24 is a novel candidate gene for non-syndromic intellectual disability. Human genetics. 2013 Oct;132(10):1177-85