Hereditary neuropathy or pain disorder
Gene: NUDT2
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
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
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Rating Amber as only 2 unrelated cases harbouring the same variant reported at presentCreated: 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: LiteratureCreated: 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
Gene: nudt2 has been classified as Amber List (Moderate Evidence).
Publications for gene: NUDT2 were set to 27431290; 30059600; 33058507
gene: NUDT2 was added gene: NUDT2 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature watchlist, founder-effect tags were added to gene: NUDT2. Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUDT2 were set to 27431290; 30059600; 33058507 Phenotypes for gene: NUDT2 were set to Sensorimotor polyneuropathy; Muscular hypotonia; Intellectual disability; no OMIM number Review for gene: NUDT2 was set to AMBER