Human Genetics

, Volume 132, Issue 10, pp 1177–1185

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

  • 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
Original Investigation

DOI: 10.1007/s00439-013-1322-3

Cite this article as:
Vandewalle, J., Bauters, M., Van Esch, H. et al. Hum Genet (2013) 132: 1177. doi:10.1007/s00439-013-1322-3

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.

Supplementary material

439_2013_1322_MOESM1_ESM.doc (54 kb)
Supplementary material 1 (DOC 54 kb)
439_2013_1322_MOESM2_ESM.tif (674 kb)
Fig. S1. Pedigree of the family with the polymorphic deletion in SLC25A43. A. Family of individual D, who presents with ID, in whom the deletion including exons 1 to 3 of SLC25A43 was detected. This deletion was also present in his healthy mother (I.2) and older brother (II.1). B. Detailed view of the oligo-array data at the SLC25A43 locus (bottom right) and zoomed-in view (top) obtained for individual D showing the location and extent of the microdeletion at Xq24. The deletion removes part of SLC25A43 but does not include SLC25A5. Positions here are based on UCSC Hg18. Supplementary material 2 (TIFF 673 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Joke Vandewalle
    • 1
    • 2
  • Marijke Bauters
    • 1
    • 2
  • Hilde Van Esch
    • 3
  • Stefanie Belet
    • 1
    • 2
  • Jelle Verbeeck
    • 1
    • 2
  • Nathalie Fieremans
    • 1
    • 2
  • Maureen Holvoet
    • 3
  • Jodie Vento
    • 4
  • Ana Spreiz
    • 5
  • Dieter Kotzot
    • 5
  • Edda Haberlandt
    • 6
  • Jill Rosenfeld
    • 7
  • Joris Andrieux
    • 8
  • Bruno Delobel
    • 9
  • Marie-Bertille Dehouck
    • 9
  • Koen Devriendt
    • 3
  • Jean-Pierre Fryns
    • 3
  • Peter Marynen
    • 2
  • Amy Goldstein
    • 4
  • Guy Froyen
    • 1
    • 2
  1. 1.Human Genome LaboratoryVIB Center for the Biology of DiseaseLeuvenBelgium
  2. 2.Human Genome Laboratory, Department of Human GeneticsKU LeuvenLeuvenBelgium
  3. 3.Center for Human GeneticsUniversity Hospitals Leuven, KU LeuvenLeuvenBelgium
  4. 4.Division of Child NeurologyChildren’s Hospital of PittsburghPittsburghUSA
  5. 5.Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical PharmacologyInnsbruck Medical UniversityInnsbruckAustria
  6. 6.Clinical Department of PediatricsInnsbruck Medical UniversityInnsbruckAustria
  7. 7.Signature Genomic LaboratoriesPerkinElmer, IncSpokaneUSA
  8. 8.Institute of Genetic MedicineJeanne-de-Flandre HospitalCHRU de LilleFrance
  9. 9.Centre de Génétique ChromosomiqueHôpital Saint-Vincent, GHICLLilleFrance

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