Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor

Bryn D. Webb, Anthony Evans, Thomas P. Naidich, Lynne M. Bird, Sumit Parikh, Meilin Fernandez Garcia, Lindsay B. Henderson, Francisca Millan, Yue Si, Kristen J. Brennand, Peter Hung, Janet C. Rucker, Patricia G. Wheeler, Eric E. Schadt

Research output: Contribution to journalArticlepeer-review

Abstract

De novo, heterozygous, loss-of-function variants were identified in Pou domain, class 4, transcription factor 1 (POU4F1) via whole-exome sequencing in four independent probands presenting with ataxia, intention tremor, and hypotonia. POU4F1 is expressed in the developing nervous system, and mice homozygous for null alleles of Pou4f1 exhibit uncoordinated movements with newborns being unable to successfully right themselves to feed. Head magnetic resonance imaging of the four probands was reviewed and multiple abnormalities were noted, including significant cerebellar vermian atrophy and hypertrophic olivary degeneration in one proband. Transcriptional activation of the POU4F1 p.Gln306Arg protein was noted to be decreased when compared with wild type. These findings suggest that heterozygous, loss-of-function variants in POU4F1 are causative of a novel ataxia syndrome.

Original languageEnglish
Pages (from-to)685-693
Number of pages9
JournalHuman Mutation
Volume42
Issue number6
DOIs
StatePublished - Jun 2021

Keywords

  • POU4F1
  • ataxia
  • intention tremor
  • paroxysmal tonic upgaze

Fingerprint

Dive into the research topics of 'Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor'. Together they form a unique fingerprint.

Cite this