Adult onset neurodegenerative disorder

Gene: CHMP2B

Comment on phenotypes: Previous phenotypes:
familial frontotemporal lobar degeneration (ALS17);Dystonia;Frontotemporal Dementia;Frontotemporal dementia and/or amyotrophic lateral sclerosis 1;Dementia, familial, nonspecific, 600795;Dementia, familial, nonspecific, 600795Amyotrophic lateral sclerosis 17, 614696;Amyotrophic lateral sclerosis 17, 614696

Created: 29 Mar 2021, 9:29 a.m. | Last Modified: 29 Mar 2021, 9:29 a.m.

Panel Version: 2.59

Green List (high evidence)

frontotemporal dementia mapping to chromosome 3 is caused by heterozygous mutation in the CHMP2B gene. At least 3 cases - green

Created: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.

Panel Version: 1.99

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
familial frontotemporal lobar degeneration (ALS17); Dystonia; Frontotemporal Dementia; Frontotemporal dementia and/or amyotrophic lateral sclerosis 1; Dementia, familial, nonspecific, 600795; Dementia, familial, nonspecific, 600795Amyotrophic lateral sclerosis 17, 614696; Amyotrophic lateral sclerosis 17, 614696

Green List (high evidence)

Onset in adulthood

Created: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.

Panel Version: 1.72

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• 16041373
• 17956895

Variants in this GENE are reported as part of current diagnostic practice

I don't know

Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group. All the green and amber, except for the genes with triplet repeats, were reviewed.

Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.

Panel Version: 1.101

Comment: - PMID: 20352044 conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype.

Created: 23 Jul 2019, 5:30 p.m. | Last Modified: 23 Jul 2019, 5:30 p.m.

Panel Version: 1.78

Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.

Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.

Panel Version: 1.74

Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.

Created: 23 Apr 2019, 5:35 p.m. | Last Modified: 23 Jul 2019, 5:30 p.m.

Panel Version: 1.78

Green List (high evidence)

Variants in this GENE are reported as part of current diagnostic practice