title: The mitochondrial solute carrier SLC25A5 at Xq24 is a novel candidate gene for non-syndromic intellectual disability.
abstract: 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.
authors.affiliation: Human Genome Laboratory, VIB Center for the Biology of Disease, Leuven, Belgium.
authors.forename: Joke
authors.initials: J
authors.lastname: Vandewalle
authors.forename: Marijke
authors.initials: M
authors.lastname: Bauters
authors.forename: Hilde
authors.initials: H
authors.lastname: Van Esch
authors.forename: Stefanie
authors.initials: S
authors.lastname: Belet
authors.forename: Jelle
authors.initials: J
authors.lastname: Verbeeck
authors.forename: Nathalie
authors.initials: N
authors.lastname: Fieremans
authors.forename: Maureen
authors.initials: M
authors.lastname: Holvoet
authors.forename: Jodie
authors.initials: J
authors.lastname: Vento
authors.forename: Ana
authors.initials: A
authors.lastname: Spreiz
authors.forename: Dieter
authors.initials: D
authors.lastname: Kotzot
authors.forename: Edda
authors.initials: E
authors.lastname: Haberlandt
authors.forename: Jill
authors.initials: J
authors.lastname: Rosenfeld
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.forename: Bruno
authors.initials: B
authors.lastname: Delobel
authors.forename: Marie-Bertille
authors.initials: MB
authors.lastname: Dehouck
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Peter
authors.initials: P
authors.lastname: Marynen
authors.forename: Amy
authors.initials: A
authors.lastname: Goldstein
authors.forename: Guy
authors.initials: G
authors.lastname: Froyen
mesh_terms: D033742:Adenine Nucleotide Translocator 2 / Q000235:genetics / Q000378:metabolism*; D020087:Alu Elements; D001483:Base Sequence; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002675:Child, Preschool; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010375:Pedigree; D049951:X Chromosome Inactivation
chemical_list: D033742:Adenine Nucleotide Translocator 2