Genes in panel

Ataxia and cerebellar anomalies - narrow panel

Gene: POU4F1

Amber List (moderate evidence)

POU4F1 (POU class 4 homeobox 1)
EnsemblGeneIds (GRCh38): ENSG00000152192
EnsemblGeneIds (GRCh37): ENSG00000152192
OMIM: 601632, Gene2Phenotype
POU4F1 is in 1 panel

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is sufficient evidence to promote this gene to Green at the next GMS panel update - sufficient number of unrelated cases (>3), supported by an animal model (see details below)
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Webb et al. 2021 (PMID:33783914) identified four unrelated individuals with different de novo POU4F1 variants. All presented with ataxia, hypotonia, and intention tremor. 3/4 also had strabismus and a history of paroxysmal tonic upgaze. Pou4f1−/− mice are known to have uncoordinated movements consistent with the ataxia phenotype seen in this patient cohort.

POU4F1 is associated with a relevant phenotype in OMIM (Ataxia, intention tremor, and hypotonia syndrome, childhood-onset, MIM# 619352) but is not yet listed in G2P.
Created: 22 Jun 2021, 11:06 a.m. | Last Modified: 22 Jun 2021, 11:06 a.m.
Panel Version: 2.210

Zornitza Stark (Australian Genomics)

Green List (high evidence)

4 unrelated probands presenting with paediatric onset ataxia, intention tremor, and hypotonia, with de novo loss of function variants, and supporting null mouse model.
Sources: Literature
Created: 11 Jun 2021, 10:31 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) , MIM#619352

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Ataxia, intention tremor, and hypotonia syndrome, childhood-onset, OMIM:619352
Tags
Q2_21_rating
OMIM
601632
Clinvar variants
Variants in POU4F1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

22 Jun 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: POU4F1.

22 Jun 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: pou4f1 has been classified as Amber List (Moderate Evidence).

22 Jun 2021, Gel status: 0

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: POU4F1 were changed from Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) , MIM#619352 to Ataxia, intention tremor, and hypotonia syndrome, childhood-onset, OMIM:619352

11 Jun 2021, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: POU4F1 was added gene: POU4F1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: POU4F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POU4F1 were set to 33783914; 8876243 Phenotypes for gene: POU4F1 were set to Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) , MIM#619352 Review for gene: POU4F1 was set to GREEN gene: POU4F1 was marked as current diagnostic