Skeletal dysplasia
Gene: UNC45A
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 6 Mar 2022, 6:30 p.m. | Last Modified: 6 Mar 2022, 6:30 p.m.
Panel Version: 2.184
Copied this gene from the Osteogenesis imperfecta panel, as all green genes on that panel should also be green on the Skeletal dysplasia panelCreated: 25 Sep 2021, 1:43 p.m. | Last Modified: 25 Sep 2021, 1:43 p.m.
Panel Version: 2.126
Comment on list classification: Promoting this gene from grey to amber, with recommendation for green rating following GMS review. 2 unrelated families with bone fragility and biallelic variants in this gene reported in the literature, plus another case reported by an NHS laboratory.Created: 18 Aug 2021, 3:43 p.m. | Last Modified: 18 Aug 2021, 3:43 p.m.
Panel Version: 2.19
Associated with Osteootohepatoenteric syndrome #619377 (AR) in OMIM.
As expert reviewers note, PMID: 29429573 (Esteve et al 2018) report 4 individuals from 3 families with compound het missense and nonsense variants in UNC45A. In 2 of the families bone fragility is reported as part of the phenotype. Patient lymphoblastoid cells showed a 70-93% decrease in abundance in UNC45A protein compared to controls.
Additional case with bone fragility/osteopenia reported by Julia Baptista brings the number of cases with this phenotype to three.Created: 18 Aug 2021, 3:42 p.m. | Last Modified: 18 Aug 2021, 3:42 p.m.
Panel Version: 2.18
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Osteootohepatoenteric syndrome, OMIM:619377
Publications
In addition to the three families reported by Esteve et al 2018, we are aware of two additional patients with biallelic UNC45A variants. Only one had bone fragility/osteopenia, but both presented with cholestasis and diarrhoea (in one case this was congenital whereas in the other it developed early in life).Created: 19 Feb 2021, 6:07 p.m. | Last Modified: 19 Feb 2021, 6:07 p.m.
Panel Version: 2.13
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
cholestasis; diarrhea; bone fragility
Publications
Variants in this GENE are reported as part of current diagnostic practice
Bone fragility is present in 3 cases from two families and is not present in another case with biallelic variants. In vitro functional assays suggest loss-of-function mechanism of disease. In vivo zebrafish assays demonstrate defects in gut development and bone fragility doesn't appear to be assessed. Emerging gene-disease association, uncertain if bone fragility is a consistent/prominent feature of the phenotype yet.
Sources: Expert listCreated: 27 Jul 2020, 12:16 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
cholestasis; congenital diarrhea; impaired hearing; bone fragility
Publications
Tag Q3_21_rating was removed from gene: UNC45A. Tag Q3_21_NHS_review was removed from gene: UNC45A.
Source Expert Review Green was added to UNC45A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: UNC45A was added gene: UNC45A was added to Skeletal dysplasia. Sources: Expert list,Expert Review Amber Q3_21_rating, Q3_21_NHS_review tags were added to gene: UNC45A. Mode of inheritance for gene: UNC45A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UNC45A were set to 29429573 Phenotypes for gene: UNC45A were set to Osteootohepatoenteric syndrome, OMIM:619377