Ataxia and cerebellar anomalies - narrow panel

Gene: NPTX1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 10:01 a.m. | Last Modified: 11 Oct 2023, 10:01 a.m.

Panel Version: 4.37

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on classification: This gene should be rated Green as there are eight unrelated cases identified with four different heterozygous variants reported with cerebellar ataxia, out of which seven are adult-onset. This is also supported by functional studies from PMID:34788392.

PMID:34788392 reported a large multigenerational family in which 9 members and 6 additional patients from four families harboured c.1165G>A/ p.Gly389Arg variant, while one patient from another unrelated family harboured c.980A>G/ p.Glu327Gly variant. All these patients were reported with late-onset ataxia among several other clinical manifestations. PMID:35285082 reported an additional male patient with slowly progressive late-onset ataxia was identified with a novel missense variant c.428G>T/ p.Arg143Leu. However, PMID:35560436 reported a six years old girl with early-onset ataxia and it harboured a novel missense variant, c.1109A>G/ p.Gln370Arg.

This gene is associated with Spinocerebellar ataxia 50 (MIM #620158) in OMIM.

Created: 6 Feb 2023, 5:40 p.m. | Last Modified: 6 Feb 2023, 5:40 p.m.

Panel Version: 3.35

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spinocerebellar ataxia 50, OMIM:620158

Publications

• 34788392
• 35285082
• 35288776
• 35560436

Green List (high evidence)

Multiple individiuals with de novo or inherited (segregating with the phenotype) NPTX1 reported in the literature with both late and infantile-onset ataxia. Enough evidence for green.

The phenotype is described in 34788392 as:
"The NPTX1-associated phenotype consists of a late-onset, slowly progressive, cerebellar ataxia, with downbeat nystagmus, cognitive impairment reminiscent of cerebellar cognitive affective syndrome, myoclonic tremor and mild cerebellar vermian atrophy on brain imaging."
Sources: Literature

Created: 15 Dec 2022, 11:26 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Ataxia

Publications

• 34788392
• 35285082
• 35560436

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