Hereditary neuropathy or pain disorder
Gene: BAG3
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.
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 neuropathyCreated: 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
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Included in dilated cardiomyopathy panel; not (primarily) a CMT geneCreated: 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.
Complex phenotype, not pure CMT
PMID 30145633, 28224639, 22734098 also report assoc so prob should be greenCreated: 9 Dec 2015, 8:49 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Complex phenotype, not pure CMTCreated: 8 Dec 2015, 3:05 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: bag3 has been classified as Amber List (Moderate Evidence).
gene: BAG3 was added gene: BAG3 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,Emory Genetics Laboratory,UKGTN,Expert Review Red,South West GLH Mode of inheritance for gene: BAG3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: BAG3 were set to 22734908; 28754666 Phenotypes for gene: BAG3 were set to Myopathy, myofibrillar, 6 612954; Cardiomyopathy, dilated, 1HH, 613881