Ataxia and cerebellar anomalies - narrow panel

Gene: UBTF

Green List (high evidence)

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

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 9 unrelated individuals from different ethnic backgrounds in literature with neuroregression including ataxia as an early feature due to a recurrent variant in this gene (PMIDs: 28777933; 29300972; 30517966; 31931739)

Created: 6 May 2021, 3:47 p.m. | Last Modified: 6 May 2021, 3:47 p.m.

Panel Version: 2.159

UBTF is associated with a relevant phenotype in OMIM and has a 'probable' disease confidence rating for 'Childhood-Onset Neurodegeneration' ​in Gene2Phenotype.

- PMID: 28777933 (2017) - 7 unrelated individuals with developmental regression starting at 2.5–7 years and the same de novo heterozygous variant, (c.628G>A, p.Glu210Lys) in UBTF. Variable movement phenotype were observed including ataxia in 3/7 subjects.

- PMID: 29300972 (2018) - 4 patients developed neuroregression at 2.5–3 years including ataxia in all cases due to the same (c.628G>A, p.Glu210Lys) in UBTF as previously described

- PMID: 30517966 (2018) - Single patient described with the recurrent c.628G>A variant and severe progressive neurodegeneration. He was said to have severe ataxia by age 4.

- PMID: 31931739 (2020) - Single individual reported presenting neurodegeneration with ataxia of limbs and gait as an early feature, associated with UBTF c.628G>A.

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The recurrent variant has been functionally validated in several studies and has been shown to confer a gain-of-function effect.

Created: 6 May 2021, 3:43 p.m. | Last Modified: 6 May 2021, 3:43 p.m.

Panel Version: 2.158

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodegeneration, childhood-onset, with brain atrophy, OMIM:617672

Publications

• 28777933
• 29300972
• 30517966
• 31931739

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Green List (high evidence)

Paediatric ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants.
Sources: Expert list

Created: 13 Sep 2020, 7:55 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodegeneration, childhood-onset, with brain atrophy MIM#617672

Publications

• 29300972

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