Osteogenesis imperfectaGene: MESD
Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.
Created: 19 Oct 2020, 2:56 p.m. | Last Modified: 19 Oct 2020, 2:56 p.m.
Panel Version: 2.7
Comment on list classification: Changing rating from red to green. More than three families reported, with plausible disease causing variants.
Created: 13 May 2020, 12:17 p.m. | Last Modified: 13 May 2020, 12:17 p.m.
Panel Version: 2.6
Gene suggested by Alistair Pagnamenta.
Associated with Osteogenesis imperfecta, type XX, #618644 (AR) in OMIM.
PMID: 31564437 Moosa et al 2019. Report 5 independent consanguineous families with a progressively deforming type of OI. Using WES and prioritising homozygous variants, they found all patients were homozygous for a mutation in the third and final exon of MESD. Parents were heterozygous. Variants were not common polymorphisms. 4 different truncation or frameshift variants were found. In mice, homozygous loss-of-function Mesd mutations cause embryonic lethality during gastrulation (PubMed: 11247670). In functional studies the MESD mutations produce hypomorphic alleles whose failure to remain within the ER significantly reduces but does not completely eliminate LRP5 and LRP6 trafficking.
Alistair Pagnamenta notes that there is a lack of sibling data.
Created: 13 May 2020, 12:16 p.m. | Last Modified: 13 May 2020, 12:18 p.m.
Panel Version: 2.6
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MESD were changed from Osteogenesis imperfecta, type XX, 618644 to Osteogenesis imperfecta, type XX, OMIM:618644; Osteogenesis imperfecta, type 20, MONDO:0032846
Gene: mesd has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: MESD.
Gene: mesd has been classified as Green List (High Evidence).
Phenotypes for gene: MESD were changed from to Osteogenesis imperfecta, type XX, 618644
gene: MESD was added gene: MESD was added to Osteogenesis imperfecta. Sources: Literature Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MESD were set to 31564437