Ataxia and cerebellar anomalies - narrow panel

Gene: PNPT1

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:10 p.m. | Last Modified: 24 Feb 2025, 5:10 p.m.

Panel Version: 7.18

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There are four unrelated cases with spinocerebellar ataxia 25 (MIM # 608703), although there is evidence of incomplete penetrance in one of them. There is also functional studies available in support of the association. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 4 Nov 2024, 3:14 p.m. | Last Modified: 4 Nov 2024, 3:14 p.m.

Panel Version: 7.3

PMID:14705117 reported a large family from Southeastern France with spinocerebellar ataxia with sensory involvement. Age at onset ranged from 17 months to 39 years, although most of those affected had onset in childhood. Cerebellar ataxia was always present and many patients had peripheral sensory neuropathy.

PMID:35411967 reported the identification of heterozygous splice site variants in PNPT1 in the above reported family from Southeastern France and from a 3-generation Australian family with spinocerebellar ataxia and sensory neuropathy reported in this study. There was evidence of incomplete penetrance in the Australian family, as two carriers in this family had sensory neuropathy without ataxia or cerebellar atrophy in their thirties. A 40-year-old French patient was also reported with heterozygous frameshift PNPT1 variant, who had onset of deafness shortly after birth and onset of gait ataxia at 23 years of age. This patient inherited the variant from an asymptomatic 80+ years old father.

PMID:37935417 reported the identification of a novel PNPT1 variant in a 3-year-old child with spinocerebellar ataxia. The child had cerebellar atrophy and psychomotor delay. At a follow up at 6 years of age, the symptoms had worsened and also presented with axonal sensory neuropathy.

Monoallelic variants in this gene have been associated with relevant phenotypes in OMIM (MIM #608703), but not in Gene2Phenotype.
Sources: Literature

Created: 4 Nov 2024, 3:10 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spinocerebellar ataxia 25, OMIM:608703

Publications

• 14705117
• 35411967
• 37935417