A missense variant in the nuclear export signal of the FMR1 gene causes intellectual disability

Shimriet Zeidler, Lies-anne Severijnen, Helen Boer, Esmay van der Toorn, CAL Ruivenkamp, EK Bijlsma, Rob Willemsen

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability and autism spectrum disorders. Mostly, FXS is caused by transcriptional silencing of the FMR1 gene due to a repeat expansion in the 5′ UTR, and consequently lack of the protein product FMRP. However, in rare cases FXS is caused by other types of variants in the FMR1 gene. We describe a missense variant in the FMR1 gene, identified through whole-exome sequencing, in a boy with intellectual disability and behavioral problems. The variant is located in the FMRP's nuclear export signal (NES). We performed expression and localization studies of the variant in hair roots and HEK293 cells. Our results show normal expression but significant retention of the FMRP in the cells’ nucleus. This finding suggests a possible FMRP reduction at its essential functional sites in the dendrites and the synaptic compartments and possible interference of other cellular processes in the nucleus. Together, this might lead to a FXS phenotype in the boy.

Original languageEnglish
Article number145298
JournalGene
Volume768
DOIs
Publication statusPublished - 2021

Fingerprint

Dive into the research topics of 'A missense variant in the nuclear export signal of the FMR1 gene causes intellectual disability'. Together they form a unique fingerprint.

Cite this