Hereditary Neuropathy_CMT - isolated

Gene: BSCL2

Green List (high evidence)

Definitive gene-disease association classified by ClinGen - https://search.clinicalgenome.org/CCID:004292

The mechanism of disease appears to be heterozygous toxic gain of function.
"Expression of the BSCL2 mutants, N88S and S90L resulted in the accumulation of toxic aggregates in cells and activation of autophagy, an emerging common pathomechanism in inherited peripheral neuropathies"

Created: 8 Apr 2024, 11:38 p.m. | Last Modified: 8 Apr 2024, 11:38 p.m.

Panel Version: 1.39

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
distal hereditary motor neuropathy MONDO:0018894

Publications

• PMID: 25832430
• 23470542
• https://search.clinicalgenome.org/CCID:004292

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Green List (high evidence)

Distal hereditary motor neuronopathy type VC (dHMN5C or HMN5C) is an autosomal dominant neurologic disorder characterized by distal muscle weakness and atrophy affecting both the upper and lower limbs, resulting in difficulty walking and poor fine hand motor skills. Some patients show spasticity and hyperreflexia, mainly of the lower limbs: these features overlap with those observed in Silver syndrome, an allelic disorder. In addition, some patients with BSCL2 mutations show features of Charcot-Marie-Tooth type 2 (CMT2) with distal sensory impairment.

HMN5C, Silver syndrome (SPG17), and features of axonal sensorimotor peripheral neuropathy (CMT2) thus represent a phenotypic spectrum associated with heterozygous mutations in the BSCL2 gene. Individuals with the same mutation may manifest features consistent with any of those disorders; variability is even observed within the same family.

Multiple families reported.

Created: 2 May 2021, 11:21 p.m. | Last Modified: 2 May 2021, 11:21 p.m.

Panel Version: 0.77

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neuropathy, distal hereditary motor, type VC, MIM# 619112

Publications

• 14981520
• 15732094