Distal myopathies

Gene: NEB

Green List (high evidence)

Comment on mode of inheritance: As there is sufficient evidence available for the association of monoallelic intragenic deletions in NEB gene with a milder distal myopathy phenotype, the MOI should be updated to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' in the next GMS update.

Created: 14 Jul 2025, 10:28 a.m. | Last Modified: 14 Jul 2025, 10:28 a.m.

Panel Version: 6.8

PMID:40517164 reported the identification of eight unique, large in-frame deletions encompassing 52-97 exons in either heterozygous (10 families) or mosaic (2 families) state in 12 unrelated families with a distal myopathy phenotype, of which 10 families were previously unpublished. All these patients with large dominant deletions in NEB presented with mild phenotypes and primarily distal involvement, with facial and proximal involvement along with scapular winging present in some patients.

Created: 14 Jul 2025, 10:25 a.m. | Last Modified: 14 Jul 2025, 10:25 a.m.

Panel Version: 6.5

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
distal myopathy, MONDO:0018949

Publications

• 40517164

Green List (high evidence)

Comment when marking as ready: can present with distal involvement as discussed with expert, Dr Bugiardini

Created: 20 Feb 2017, 4:43 p.m.

distal nebulin myopathy may be a differential diagnosis of distal myopathies

Created: 1 Feb 2017, 10:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nemaline myopathy 2, 256030