Ataxia and cerebellar anomalies - narrow panel
Gene: POU4F1
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 5 Feb 2023, 5:18 p.m. | Last Modified: 5 Feb 2023, 5:18 p.m.
Panel Version: 3.30
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
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: LiteratureCreated: 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
Tag Q2_21_rating was removed from gene: POU4F1.
Source Expert Review Green was added to POU4F1. Source NHS GMS was added to POU4F1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_21_rating tag was added to gene: POU4F1.
Gene: pou4f1 has been classified as Amber List (Moderate Evidence).
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
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