Hand and foot malformations

Gene: MGP

Green List (high evidence)

Four individuals from two unrelated families with two heterozygous variants in MGP, both altering the cysteine 19 residue to phenylalanine (C19F) or tyrosine (C19Y):
Family 1 (NM_000900.3:c.56G>T:p.C19F) - affected parent and two affected children harbour the variant. Third unaffected child does not harbour the variant.
Family 2 (NM_000900.3:c.56G>A:p.C19Y) - de novo variant in affected proband.

Phenotype of spondyloepiphyseal skeletal dysplasia characterized by short stature with a short trunk, diffuse platyspondyly, midface retrusion, progressive epiphyseal anomalies and brachytelephalangism.

Functional evidence to support hypothesis - heterozygous ‘knock-in’ mice expressing C19F MGP recapitulate most of the skeletal anomalies observed in the affected individuals.

Created: 7 Dec 2023, 1:23 a.m. | Last Modified: 7 Dec 2023, 1:23 a.m.

Panel Version: 0.72

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• PMID: 37675773