Hereditary neuropathy or pain disorder

Gene: BAG3

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:02 p.m. | Last Modified: 24 Feb 2025, 5:02 p.m.

Panel Version: 6.148

Numerous BAG3 variants have been associated with OMIM:612954 and OMIM:613881. Sensorimotor polyneuropathy has been associated with at least three BAG3 variants in three unrelated cases (PMID: 25208129; 30145633; 37989284; 37907725.

Created: 4 Nov 2024, 11:26 a.m. | Last Modified: 4 Nov 2024, 11:26 a.m.

Panel Version: 6.20

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

Phenotypes
Myopathy, myofibrillar, 6, OMIM:612954; myofibrillar myopathy 6, MONDO:0013061; dilated cardiomyopathy 1HH, MONDO:0013479; Cardiomyopathy, dilated, 1HH, OMIM:613881

Publications

• 37989284
• 30145633
• 37907725
• 25208129

I don't know

Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - myopathy with neuropathy / Broader phenotype - not reviewed by Alex in this round but previously reviewed as Green; myofibrillar myopathy, sufficient evidence for neuropathy?

Created: 6 Dec 2019, 2:03 p.m. | Last Modified: 6 Dec 2019, 2:03 p.m.

Panel Version: 0.31

Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.

Created: 6 Dec 2019, 2:02 p.m. | Last Modified: 6 Dec 2019, 2:02 p.m.

Panel Version: 0.31

Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 29 Apr 2019, 12:53 p.m.

I don't know

In Bristol C3s only (none with cardiac features). Doesn't currently fit PanelApp criteria for green for neuropathy. PMID:28754666 - appears to be strong segregation evidence for p.Pro209Ser in one family with neuropathy but no cardiac disease (weaker evidence in a second). PMID:22734908 - four patients with heterozygous BAG3 mutations with clinical evidence of a sensorimotor neuropathy, with predominantly axonal features on neurophysiology. Can't see funcational evidence in relation to neuropathy

Created: 29 Apr 2019, 12:30 p.m.

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

Phenotypes
Cardiomyopathy, dilated, 1HH, 613881; Myopathy, myofibrillar, 6 612954

Publications

• 28754666
• 22734908

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

Red List (low evidence)

Comment on list classification: Included in dilated cardiomyopathy panel; not (primarily) a CMT gene

Created: 8 Jul 2016, 3:40 a.m.

Comment when marking as ready: This gene will be kept as amber due to disagreement between reviewers and the complexity of the phenotype (and whether neuropathy is a primary feature caused by variants within this gene).

Created: 10 May 2016, 1:11 p.m.

Comment on list classification: Originally an amber gene, with conflicting reviews. Associated with cardiomyopathy, dilated, IHH and myopathy, myofibrillar 6 in OMIM.

Created: 4 May 2016, 8:32 a.m.

Green List (high evidence)

Further reports in assocation with PN since my last review, should now be green

Created: 20 Oct 2024, 9:09 a.m. | Last Modified: 20 Oct 2024, 9:09 a.m.

Panel Version: 5.19

Complex phenotype, not pure CMT
PMID 30145633, 28224639, 22734098 also report assoc so prob should be green

Created: 9 Dec 2015, 8:49 a.m.

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

Phenotypes
cardiomyopathy; polyneuropathy

Publications

• 30145633: 37989284: 37907725

Green List (high evidence)

Complex phenotype, not pure CMT

Created: 8 Dec 2015, 3:05 p.m.

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