Ataxia - adult onset

Gene: PNPT1

I don't know

An additional family with a heterozygous NMD-predicted variant (c.1287del Pro430Leufs*14) was identified in PMID: 37935417. A child, age of onset 3yo, with frequent falls, cerebellar signs, psychomotor delay, cerebellar atrophy and axonal sensory neuropathy was identified heterozygous for this variant. This variant was also identified in the heterozygous mother (32yo) and grandmother (63yo) who were both unaffected with normal MRIs.

Created: 16 Jul 2024, 1:08 a.m. | Last Modified: 16 Jul 2024, 1:08 a.m.

Panel Version: 1.15

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spinocerebellar ataxia 25 (MIM#608703)

Publications

• PMID: 37935417

I don't know

Three families reported with heterozygous variants and SCA25. Incomplete penetrance in one of the families. In the third family, the variant was inherited from an asymptomatic 80+ year old.

Note bi-allelic variants in this gene cause a mitochondrial disorder. Exact mechanism through which mono-allelic variants cause SCA25 not elucidated: authors speculate abnormal accumulation of mitochondrial RNA with subsequent leakage into the cytosol that may trigger a type 1 interferon response leading to neuroinflammation with neuronal dysfunction or neuronal loss.
Sources: Literature

Created: 13 Jul 2022, 11:55 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spinocerebellar ataxia 25, MIM# 608703

Publications

• 35411967

Green List (high evidence)

6 additional unrelated cases identified by Pennisi et al., 2022 (PMID: 33199448) with biallelic variants in this gene.

Created: 1 Apr 2022, 10:25 a.m. | Last Modified: 1 Apr 2022, 10:25 a.m.

Panel Version: 0.12453

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 13, OMIM:614932

Publications

• 33199448

Green List (high evidence)

Biallelic variants reported in patients with a wide clinical heterogeneity ranging from non-syndromic hearing loss to multisystemic Leigh syndrome.

Possible genotype-phenotype correlation: Combination of missense and a null allele resulting in less residual activity present with white matter abnormalities. Patients with only missense variants did not have white matter abnormalities (PMID: 28594066)

Created: 20 Feb 2020, 9:56 p.m. | Last Modified: 20 Feb 2020, 9:56 p.m.

Panel Version: 0.1415

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934)

Publications

• PMID:31752325
• PMID: 30244537
• PMID: 28594066
• PMID: 28645153