Hereditary neuropathy or pain disorder
Gene: VAPB
The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.Created: 10 Oct 2023, 6:06 p.m. | Last Modified: 10 Oct 2023, 6:06 p.m.
Panel Version: 3.58
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Comment on list classification: There is sufficient evidence (>3 unrelated cases & functional studies from mouse models) for this gene to be promoted to GREEN at the next major review.Created: 30 Apr 2023, 11:32 a.m. | Last Modified: 30 Apr 2023, 11:32 a.m.
Panel Version: 3.18
PMID:15372378 reported seven kindreds with patients affected by an MND but had different clinical courses: three had late-onset slowly progressive atypical amyotrophic lateral sclerosis (ALS), three had a late-onset Spinal muscular atrophy (SMA) type Finkel (MIM #182980), and, in one kindred, some patients had typical ALS, whereas others had an atypical form of ALS. All these patients were identified with a novel missense variant ((p.Pro56Ser) in VAPB gene.
Another variant, p.Thr46Ile was identified in a patient with familial ALS from PMID:20940299, whereas it was missing in controls. PMID:28993872 reported a third variant, p.Pro56His in a Chinese family with familial ALS.
Functional studies in mouse models showed that lifelong elevation of neuronal VAPB slows the decline of neurological impairment, delayed denervation of hindlimb muscles, and prolonged survival of spinal motor neurons (PMID:28173107).
VAPB has also been associated with relevant phenotypes in OMIM (MIMs #182980 & #608627).Created: 30 Apr 2023, 11:29 a.m. | Last Modified: 30 Apr 2023, 11:29 a.m.
Panel Version: 3.15
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Spinal muscular atrophy, late-onset, Finkel type, OMIM:182980; Amyotrophic lateral sclerosis 8, OMIM:608627
Publications
p.P56S variant found in multiple families from different ethnicities but additional variant also reported; functional data.
Sources: Expert listCreated: 2 Apr 2020, 8:11 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Adult proximal spinal muscular atrophy, autosomal dominant; dHMN/dSMA; Spinal muscular atrophy, late-onset, Finkel type, MIM# 182980
Publications
Tag Q2_23_promote_green was removed from gene: VAPB.
Source Expert Review Green was added to VAPB. Source NHS GMS was added to VAPB. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_23_promote_green tag was added to gene: VAPB.
Gene: vapb has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: VAPB were changed from Adult proximal spinal muscular atrophy, autosomal dominant; dHMN/dSMA; Spinal muscular atrophy, late-onset, Finkel type, MIM# 182980 to Spinal muscular atrophy, late-onset, Finkel type, OMIM:182980; Amyotrophic lateral sclerosis 8, OMIM:608627
Publications for gene: VAPB were set to 15372378; 32162544; 28993872; 28173107; 26566915
gene: VAPB was added gene: VAPB was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Expert list Mode of inheritance for gene: VAPB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VAPB were set to 15372378; 32162544; 28993872; 28173107; 26566915 Phenotypes for gene: VAPB were set to Adult proximal spinal muscular atrophy, autosomal dominant; dHMN/dSMA; Spinal muscular atrophy, late-onset, Finkel type, MIM# 182980 Review for gene: VAPB was set to GREEN