Congenital myopathy
Gene: UNC45BRemoved the to_be_confirmed_NHSE tag because this gene has been re-reviewed by an NHSE clinician (Anna Sarkozy) and so should be included in the next data review. Tag added in March 2022, re-reviewed in Nov 2022, removed June 2023.Created: 7 Jun 2023, 12:42 p.m. | Last Modified: 7 Jun 2023, 12:42 p.m.
Panel Version: 4.29
12 patients from 10 unrelated families reported in literature with bi-allelic pathogenic UNC45B gene variants. Patients were presenting a neuromuscular phenotype in keeping with a diagnosis of congenital myopathy with neonatal/childhood onset, characterised in particular by reduced foetal movements, hypotonia at birth, progressive early onset muscle weakness, mostly axial and proximal, facial weakness, ophthalmoplegia, respiratory involvement, feeding difficulties, scoliosis. published muscle MRI show a myopathic pattern. CK is normal. available Pathology indicates a structural myopathic with eccentric cores and internal nuclei. Overall, these findings, together with published functional evidence, supports the upgrade of this gene to GREEN.Created: 10 Nov 2022, 11:23 a.m. | Last Modified: 10 Nov 2022, 11:23 a.m.
Panel Version: 2.93
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
congenital myopathy; progressive myopathy with eccentric cores; core myopathy
Publications
Mode of pathogenicity
Other
Associated with relevant Myofibrillar myopathy 11 in OMIM and as strong Gen2Phen gene for UNC45B-associated Progressive Myopathy with Eccentric Cores. At least 7 variants have been reported in at least 10 unrelated families. SEgregation has been observed and functional studies suggest that reduced expression of UNC45B is associated with Myofibrillar myopathy 11. This review represents further information from subsequent case reports and the update of OMIM to allow OMIM asign a phenotype tp this gene.Created: 13 Dec 2022, 1:41 p.m. | Last Modified: 13 Dec 2022, 1:41 p.m.
Panel Version: 3.10
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.Created: 17 Mar 2022, 10:56 a.m. | Last Modified: 17 Mar 2022, 10:56 a.m.
Panel Version: 2.83
There is enough evidence for this gene to be rated GREEN at the next major review.Created: 19 Jan 2021, 6:03 p.m. | Last Modified: 19 Jan 2021, 6:03 p.m.
Panel Version: 2.20
Comment on phenotypes: UNC45B-associated Progressive Myopathy with Eccentric Cores (Gen2Phen)(https://www.ebi.ac.uk/gene2phenotype/gfd?search_type=gfd&dbID=4636). OMIM, MONDO and Orphanet have yet to list this phenotype (20210119)Created: 19 Jan 2021, 6:03 p.m. | Last Modified: 19 Jan 2021, 6:03 p.m.
Panel Version: 2.20
Comment on list classification: Not associated with relevant phenotype in OMIM (OMIM have been notified about PMID 33217308) and as probable Gen2Phen gene for UNC45B-associated Progressive Myopathy with Eccentric Cores. At least 5 variants reported in at least 6 apparently unrelated cases, together with supportive functional studies.Created: 19 Jan 2021, 5:58 p.m. | Last Modified: 19 Jan 2021, 6:03 p.m.
Panel Version: 2.20
10 individuals from 8 families reported with biallelic variants clinically manifesting with childhood-onset, progressive proximal and axial muscle weakness and various degrees of respiratory insufficiency. 4 missense variants and a +5 splice variant reported, p.Arg754Gln is recurrent. Functional studies support pathogenicity.
Sources: LiteratureCreated: 9 Dec 2020, 7:59 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Progressive Myopathy with Eccentric Cores
Publications
Tag to_be_confirmed_NHSE was removed from gene: UNC45B.
Phenotypes for gene: UNC45B were changed from Myofibrillar myopathy 11, OMIM:619178; myofibrillar myopathy 11, MONDO:0030927 to Myofibrillar myopathy 11, OMIM:619178
Tag Q4_22_promote_green tag was added to gene: UNC45B. Tag Q4_22_expert_review tag was added to gene: UNC45B. Tag Q4_22_NHS_review tag was added to gene: UNC45B.
Phenotypes for gene: UNC45B were changed from Progressive Myopathy with Eccentric Cores to Myofibrillar myopathy 11, OMIM:619178; myofibrillar myopathy 11, MONDO:0030927
Publications for gene: UNC45B were set to 33217308
Tag to_be_confirmed_NHSE tag was added to gene: UNC45B.
Gene: unc45b has been classified as Amber List (Moderate Evidence).
Tag for-review was removed from gene: UNC45B.
Source Expert Review Green was added to UNC45B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: UNC45B were changed from Progressive Myopathy with Eccentric Cores to Progressive Myopathy with Eccentric Cores
Gene: unc45b has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: UNC45B.
gene: UNC45B was added gene: UNC45B was added to Congenital myopathy. Sources: Literature Mode of inheritance for gene: UNC45B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UNC45B were set to 33217308 Phenotypes for gene: UNC45B were set to Progressive Myopathy with Eccentric Cores Review for gene: UNC45B was set to GREEN