Amyotrophic lateral sclerosis/motor neuron disease

Gene: CHMP2B

Comment on list classification: Kept as red due to expert review. Not present on the NHNN NGS gene panel for ALS, and only found in one source under the ALS phenotype.

Created: 15 Jun 2016, 1:44 p.m.

Red List (low evidence)

Defects in CHMP2B were originally reported in autosomal dominant FTD. The G>C single nucleotide change in the acceptor splice site of exon 6 of CHMP2B affected mRNA splicing, resulting in two aberrant transcripts: inclusion of the 201-bp intronic sequence between exons 5 and 6, or a short deletion of 10bp from the 5′ end of exon 6. Expression of mutant CHMP2B protein in cells resulted in aberrant structures dispersed throughout the cytosol and the ectopic expression of CHMP2BIntron5 in cortical neurons caused dendritic retraction prior to neurodegeneration.

Sequence analysis of the entire coding region and intron/exon boundaries of CHMP2B from 433 ALS cases identified point mutations in four cases (0.9%)
Miss-sense variants only identified. The phenotype appears to represent a lower motor neuron variant in these cases, however, the present study has not been able to document the segregation of CHMP2B in multiple affected members of specific pedigrees in ALS. CMMP2B may act as a modifier.

Created: 9 Jun 2016, 8:15 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Amyotrophic Lateral Sclerosis, Frontotemporal Dementia

Publications

• 20352044

Mode of pathogenicity
Other