De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females

R. Webster, M. T. Cho, K. Retterer, F. Millan, C. Nowak, J. Douglas, A. Ahmad, G. V. Raymond, M. R. Johnson, A. Pujol, A. Begtrup, D. Mcknight, O. Devinsky, W. K. Chung

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Intellectual disability (ID) affects about 3% of the population and has a male gender bias. Of at least 700 genes currently linked to ID, more than 100 have been identified on the X chromosome, including KIAA2022. KIAA2022 is located on Xq13.3 and is expressed in the developing brain. The protein product of KIAA2022, X-linked Intellectual Disability Protein Related to Neurite Extension (XPN), is developmentally regulated and is involved in neuronal migration and cell adhesion. The clinical manifestations of loss-of-function KIAA2022 mutations have been described previously in 15 males, born from unaffected carrier mothers, but few females. Using whole-exome sequencing, we identified a cohort of five unrelated female patients with de novo probably gene damaging variants in KIAA2022 and core phenotypic features of ID, developmental delay, epilepsy refractory to treatment, and impaired language, of similar severity as reported for male counterparts. This study supports KIAA2022 as a novel cause of X-linked dominant ID, and broadens the phenotype for KIAA2022 mutations.

Original languageEnglish (US)
Pages (from-to)756-763
Number of pages8
JournalClinical Genetics
Issue number5
StatePublished - May 1 2017

Bibliographical note

Funding Information:
We gratefully acknowledge the contributions of the individuals with KIAA2022 variants and their families. This work was supported in part by funding from the Simons Foundation.

Publisher Copyright:
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


  • KIAA2022
  • autism
  • intellectual disability
  • seizures
  • whole-exome sequencing


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