Skeletal dysplasia

Gene: MGP

Green List (high evidence)

Comment on mode of inheritance: As there is sufficient evidence available (two unrelated cased and functional studies) for the association of monoallelic MGP variants with spondyloepiphyseal dysplasia, the MOI should be updated from 'BIALLELIC, autosomal or pseudoautosomal' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS review.

Created: 24 Jan 2024, 12:43 p.m. | Last Modified: 24 Jan 2024, 12:43 p.m.

Panel Version: 4.48

PMID:37923733 reported four individuals from two unrelated families with two different heterozygous MGP variants affecting Cys 19 residue (family 1: p.Cys19Phe; family 2: p.Cys19Tyr) and with previously undescribed spondyloepiphyseal dysplasia characterized by short stature with a short trunk, diffuse platyspondyly, midface retrusion, progressive epiphyseal anomalies and brachytelephalangism. In addition, functional evidence from heterozygous ‘knock-in’ mice expressing Cys19Phe MGP recapitulate most of the skeletal anomalies observed in the affected individuals.

Although phenotype caused by biallelic MGP variants are already reported in both OMIM (MIM #245150) and Gene2Phenotype, phenotype caused by monoallelic variants are not yet reported in either resources.

Created: 24 Jan 2024, 12:36 p.m. | Last Modified: 24 Jan 2024, 12:40 p.m.

Panel Version: 4.45

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Keutel syndrome, OMIM:245150; spondyloepiphyseal dysplasia, MONDO:0016761

Publications

• 37923733

Green List (high evidence)

Chondrodysplasia punctata gp of SD - at least 3 cases; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Keutel syndrome 245150

I don't know

The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 3:01 p.m. | Last Modified: 26 Sep 2024, 3:01 p.m.

Panel Version: 6.7

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: MGP; Initial rating suggestion: green

Created: 6 Mar 2019, 11:36 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Comment when marking as ready: Numerous variants reported in this phenotype

Created: 12 Jul 2016, 9:56 a.m.

Green List (high evidence)

Tier 1

Created: 17 Jun 2016, 8:05 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Keutel syndrome (diffuse cartilage calcification, brachytelephalangism, peripheral pulmonary artery stenoses and facial dysmorphism) 245150

Variants in this GENE are reported as part of current diagnostic practice