Skeletal dysplasia

Gene: MESD

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ostoegenesis Imperfecta; Fractures

Publications

• 33596325
• 31564437

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

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

Further green review from NHS clinician, but already tagged for green rating in next GMS review.

Created: 15 Sep 2021, 1:59 p.m. | Last Modified: 15 Sep 2021, 1:59 p.m.

Panel Version: 2.26

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

Publications

• 31564437