Hereditary neuropathy or pain disorder

Gene: NUDT2

Green List (high evidence)

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

Created: 24 Feb 2025, 5:02 p.m. | Last Modified: 24 Feb 2025, 5:02 p.m.

Panel Version: 6.148

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Recent publication attached showing peripheral neuropathy in several new unrelated individuals so should therefore be green and included in panel

Created: 20 Oct 2024, 10:19 a.m. | Last Modified: 20 Oct 2024, 10:19 a.m.

Panel Version: 5.19

Recent publication attached showing peripheral neuropathy in several new unrelated individuals so should therefore be green and included in panel

Created: 20 Oct 2024, 10:18 a.m. | Last Modified: 20 Oct 2024, 10:18 a.m.

Panel Version: 5.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
developmental delay; neuropathy

Publications

• 38141063

Green List (high evidence)

Comment on list classification: There is sufficient evidence available now for the promotion of this gene to green rating in the next GMS update.

Created: 24 Oct 2024, 9:54 a.m. | Last Modified: 24 Oct 2024, 9:54 a.m.

Panel Version: 5.77

As reviewed by Alexander Rossor, PMID:38141063 reported 18 patients from 10 different families with a neurological disorder typified by intellectual disability, motor developmental delay and gait disturbance and they were all identified with biallelic NUDT2 variants. 71% of these patients had sensorimotor neuropathy.

Created: 24 Oct 2024, 9:53 a.m. | Last Modified: 24 Oct 2024, 9:53 a.m.

Panel Version: 5.74

Comment on gene rating: As there are only two unrelated cases with neuropathy, this gene should stay as AMBER for now.

PMID:33058507 reported two unrelated families with homozygous frameshift variant (c.186delA/ p.A63Qfs*3) in NUDT2 gene presenting with global developmental delay, intellectual disability, and sensorimotor neuropathy with associated distal weakness.

The cases reported in PMIDs: 27431290& 30059600 were identified with biallelic NUDT2 variants and presented with a neurodevelopmental disorder characterized by hypotonia, poor sucking in the neonatal period/ infancy, delayed motor and language development and global developmental delay with impaired intellectual development. However, these patients were not reported with neuropathy.

Created: 16 Apr 2023, 10:29 p.m. | Last Modified: 16 Apr 2023, 10:29 p.m.

Panel Version: 3.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual developmental disorder with or without peripheral neuropathy, OMIM:619844

Publications

• 27431290
• 30059600
• 33058507
• 38141063

Green List (high evidence)

Eight families reported altogether, though some have same founder variant. Four had polyneuropathy as part of the phenotype.

Created: 7 Jan 2021, 10:03 a.m. | Last Modified: 7 Jan 2021, 10:03 a.m.

Panel Version: 1.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular hypotonia; Global developmental delay; Intellectual disability; Polyneuropathy

Publications

• 33058507
• 27431290
• 30059600
• 33058507

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

I don't know

Comment on list classification: Rating Amber as only 2 unrelated cases harbouring the same variant reported at present

Created: 3 Nov 2020, 4:56 p.m. | Last Modified: 3 Nov 2020, 4:56 p.m.

Panel Version: 1.15

Comment on tags: added 'founder-effect' tag - although authors state that they do not believe p.Ala63GlnfsTer3 to be a founder variant (one family of Mexican descent while the other of Cajun descent), this was not confirmed by haplotype analysis. Also added 'watchlist' tag in anticipation of further publications/clinical evidence to support association with this phenotype.

Created: 3 Nov 2020, 4:55 p.m. | Last Modified: 3 Nov 2020, 4:55 p.m.

Panel Version: 1.14

- PMID: 33058507 (2020) - Three patients from two families harbouring the same homozygous variant (c.186del, p.Ala63GlnfsTer3). Affected individuals present distal upper and lower extremity weakness due to a sensorimotor polyneuropathy with demyelinating and/or axonal features.
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A further 4 Saudi families (7 affected individuals) with a different homozygous NUDT2 variant (c.34C> T, p.Arg12) have been published elsewhere (PMID: 27431290, 30059600), however neuropathy was not reported in these cases.
Sources: Literature

Created: 3 Nov 2020, 4:42 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sensorimotor polyneuropathy; Muscular hypotonia; Intellectual disability; no OMIM number

Publications

• 27431290
• 30059600
• 33058507