Congenital muscular dystrophy and congenital myopathy

Gene: UNC45B

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 3:45 p.m. | Last Modified: 2 May 2024, 3:45 p.m.

Panel Version: 0.229

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Removed to_be_confirmed_NHSE tag as it has been re-reviewed by an NHSE clinician.

Created: 7 Jun 2023, 12:43 p.m. | Last Modified: 7 Jun 2023, 12:43 p.m.

Panel Version: 0.184

Green List (high evidence)

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

• PMID: 33217308
• 31852522
• 35292251

Mode of pathogenicity
Other

Green List (high evidence)

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

Green List (high evidence)

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: Literature

Created: 9 Dec 2020, 7:59 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Progressive Myopathy with Eccentric Cores

Publications

• 33217308