Microdeletion of the escape genes KDM5C and IQSEC2 in a girl with severe intellectual disability and autistic features

Nathalie Fieremans, Hilde Van Esch, Thomy de Ravel, Jozef Van Driessche, Stefanie Belet, Marijke Bauters, Guy Froyen

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Intellectual disability (ID) is a very heterogeneous disorder with over 100 ID genes located on the X chromosome alone. Of these, KDM5C and IQSEC2 are located adjacent to each other at the Xp11.22 locus. While mutations in either of these genes are associated with severe ID in males, female carriers are mostly unaffected. Here, we report on a female patient with severe ID and autistic features carrying a de novo 0.4 Mb deletion containing six coding genes including KDM5C and IQSEC2. X-inactivation analysis revealed skewing in a lymphocyte-derived cell line from this patient with preferential inactivation of the mutant X chromosome. As the brain-expressed KDM5C and IQSEC2 genes escape X-inactivation, deletion of these alleles could still be detrimental despite skewing of X-inactivation. Indeed, mutations in either of both genes have been reported in a few female ID patients. Expression analysis in the patients' cell line revealed decreased KDM5C mRNA levels compared to female controls. IQSEC2 levels could not be compared due to very low expression in blood. Overall, our data suggest that heterozygous loss-of-function of the escape genes KDM5C and/or IQSEC2 can contribute to severe ID in female patients and should be taken into account in diagnostics.

Original languageEnglish
Pages (from-to)324-7
Number of pages4
JournalEuropean Journal of Medical Genetics
Volume58
Issue number5
DOIs
Publication statusPublished - 2015

Bibliographical note

Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Keywords

  • Autistic Disorder/diagnosis
  • Chromosome Deletion
  • Female
  • Gene Expression
  • Guanine Nucleotide Exchange Factors/genetics
  • Histone Demethylases/genetics
  • Humans
  • Intellectual Disability/diagnosis
  • Young Adult

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