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 journalArticle

Abstract

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)
JournalClinical Genetics
DOIs
StateAccepted/In press - 2016
Externally publishedYes

Fingerprint

Intellectual Disability
Epilepsy
Mutation
Exome
Sexism
X Chromosome
Neurites
Cell Adhesion
Genes
Proteins
Language
Mothers
Phenotype
Brain
Population
Therapeutics

Keywords

  • Autism
  • Intellectual disability
  • KIAA2022
  • Seizures
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Webster, R., Cho, M. T., Retterer, K., Millan, F., Nowak, C., Douglas, J., ... Chung, W. K. (Accepted/In press). De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females. Clinical Genetics. https://doi.org/10.1111/cge.12854

De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females. / Webster, R.; Cho, M. T.; Retterer, K.; Millan, F.; Nowak, C.; Douglas, J.; Ahmad, A.; Raymond, G. V.; Johnson, M. R.; Pujol, A.; Begtrup, A.; Mcknight, D.; Devinsky, O.; Chung, W. K.

In: Clinical Genetics, 2016.

Research output: Contribution to journalArticle

Webster, R, Cho, MT, Retterer, K, Millan, F, Nowak, C, Douglas, J, Ahmad, A, Raymond, GV, Johnson, MR, Pujol, A, Begtrup, A, Mcknight, D, Devinsky, O & Chung, WK 2016, 'De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females', Clinical Genetics. https://doi.org/10.1111/cge.12854
Webster, R. ; Cho, M. T. ; Retterer, K. ; Millan, F. ; Nowak, C. ; Douglas, J. ; Ahmad, A. ; Raymond, G. V. ; Johnson, M. R. ; Pujol, A. ; Begtrup, A. ; Mcknight, D. ; Devinsky, O. ; Chung, W. K. / De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females. In: Clinical Genetics. 2016.
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