Hereditary neuropathy
Gene: BAG3
The Neurology Specialist Test Group agreed that this gene was recommended for the WGS panel based on a broader phenotype view to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. This panel includes conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation. This panel as going to be used for R78, 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 and as a result a new panel was created https://panelapp.genomicsengland.co.uk/panels/846/ for this purpose.Created: 7 Dec 2019, 6:08 p.m. | Last Modified: 7 Dec 2019, 6:08 p.m.
Panel Version: 1.352
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
Source Expert Review Green was added to BAG3. Rating Changed from Red List (low evidence) to Green List (high evidence)
Added phenotypes Myopathy, myofibrillar, 6 612954; Cardiomyopathy, dilated, 1HH, 613881 for gene: BAG3 Publications for gene BAG3 were changed from PMID: 25728519 - we describe the first case in which cardiomyopathy and cardiac transplantation (age eight) preceded neuromuscular weakness by several years (age 12); 22734908 - we describe four patients with heterozygous BAG3 mutations with clinical evidence of a sensorimotor neuropathy, with predominantly axonal features on neurophysiology. Three patients presented with a significant neuropathy; PMID: 26545904 - Genetic testing demonstrated heterozygous mutation Pro209Leu (c.626C > T) in exon 3 of BAG3 gene causing severe myopathy and neuropathy, often associated with restrictive cardiomyopathy. to 28754666; 22734908
Source NHS GMS was added to BAG3.
Source South West GLH was added to BAG3.
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Amber List (Moderate Evidence).
Publications for BAG3 were set to PMID: 25728519 - we describe the first case in which cardiomyopathy and cardiac transplantation (age eight) preceded neuromuscular weakness by several years (age 12); 22734908 - we describe four patients with heterozygous BAG3 mutations with clinical evidence of a sensorimotor neuropathy, with predominantly axonal features on neurophysiology. Three patients presented with a significant neuropathy; PMID: 26545904 - Genetic testing demonstrated heterozygous mutation Pro209Leu (c.626C > T) in exon 3 of BAG3 gene causing severe myopathy and neuropathy, often associated with restrictive cardiomyopathy.
Publications for BAG3 were set to PMID: 25728519 - we describe the first case in which cardiomyopathy and cardiac transplantation (age eight) preceded neuromuscular weakness by several years (age 12); 22734908 - we describe four patients with heterozygous BAG3 mutations with clinical evidence of a sensorimotor neuropathy, with predominantly axonal features on neurophysiology. Three patients presented with a significant neuropathy; PMID: 26545904 - Genetic testing demonstrated heterozygous mutation Pro209Leu (c.626C > T) in exon 3 of BAG3 gene causing severe myopathy and neuropathy, often associated with restrictive cardiomyopathy.
Publications for BAG3 were set to PMID: 25728519
This gene has been classified as Amber List (Moderate Evidence).
Model of inheritance for gene BAG3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene BAG3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene BAG3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
BAG3 was added to Charcot-Marie-Tooth diseasepanel. Sources: Emory Genetics Laboratory,UKGTN
BAG3 was added to Charcot-Marie-Tooth diseasepanel. Sources: Emory Genetics Laboratory,UKGTN