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Hereditary neuropathy NOT PMP22 copy number

Gene: NEMF

Amber List (moderate evidence)

NEMF (nuclear export mediator factor)
EnsemblGeneIds (GRCh38): ENSG00000165525
EnsemblGeneIds (GRCh37): ENSG00000165525
OMIM: 608378, Gene2Phenotype
NEMF is in 2 panels

1 review

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Rating Amber but there is sufficient evidence to promote to Green at the next GMS panel update (added 'for-review' tag) - axonal neuropathy reported in all formally assessed cases (at least 4 with biallelic variants)
Created: 3 Nov 2020, 12:11 p.m. | Last Modified: 3 Nov 2020, 12:11 p.m.
Panel Version: 1.12
Comment on mode of inheritance: Set MOI to 'Biallelic' as only 1 case with a monoallelic variant described at present. The 'watchlist' tag has been added while further evidence is gathered to establish whether or not there is a wider association with monoallelic variants and disease.
Created: 3 Nov 2020, 12:09 p.m. | Last Modified: 3 Nov 2020, 12:09 p.m.
Panel Version: 1.11
Currently not associated with any phenotype in OMIM (last edited on 04/01/2017) or Gene2Phenotype.

Gene added and expert reviewed on Intellectual Disability panel:
https://panelapp.genomicsengland.co.uk/panels/285/gene/NEMF/


- PMID: 32934225 (2020) - 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M)), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M). The authors provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration.


- PMID: 33048237 (2020) - 13 affected individuals from 5 unrelated families presenting with a spectrum of central and peripheral neurological involvement. Peripheral systemic neurological manifestations such as impaired eye movements, limb weakness, and axonal polyneuropathy were found in families 1, 2 and 5 - however, only 2 sibs from family 2 had a precise diagnosis for polyneuropathies. Knockdown studies in cultured mouse primary cortical neurons showed a significant decrease in axon length and impaired synapse development.
Sources: Literature
Created: 3 Nov 2020, 12:03 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Hypotonia; Axonal neuropathy; Ataxia; Abnormal brain imaging; Global developmental delay; Intellectual disability; Kyphosis; Scoliosis; Tremor; Respiratory distress

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Hypotonia
  • Axonal neuropathy
  • Ataxia
  • Abnormal brain imaging
  • Global developmental delay
  • Intellectual disability
  • Kyphosis
  • Scoliosis
  • Tremor
  • Respiratory distress
Tags
watchlist for-review
OMIM
608378
Clinvar variants
Variants in NEMF
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 Nov 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: nemf has been classified as Amber List (Moderate Evidence).

3 Nov 2020, Gel status: 1

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: NEMF was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

3 Nov 2020, Gel status: 1

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

gene: NEMF was added gene: NEMF was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature watchlist, for-review tags were added to gene: NEMF. Mode of inheritance for gene: NEMF was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEMF were set to 32934225; 33048237 Phenotypes for gene: NEMF were set to Hypotonia; Axonal neuropathy; Ataxia; Abnormal brain imaging; Global developmental delay; Intellectual disability; Kyphosis; Scoliosis; Tremor; Respiratory distress Review for gene: NEMF was set to GREEN