Skeletal dysplasia
Gene: NPR3
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 6 Mar 2022, 5:41 p.m. | Last Modified: 6 Mar 2022, 5:41 p.m.
Panel Version: 2.176
Comment on list classification: Promoting this gene from grey to amber with a recommendation for green rating following GMS review. 3 unrelated cases with a similar phenotype and supporting functional data and mouse model.Created: 21 Jan 2021, 4:43 p.m. | Last Modified: 21 Jan 2021, 4:43 p.m.
Panel Version: 2.75
PMID: 30032985 Boudin et al 2018 - report 4 individuals from 3 unrelated families (1 Dutch, 1 Pakistani, 1 unknown ancestry) presenting with tall stature, long digits, and extra epiphyses in the hands and feet. WES was used in 2 families and targeted NPR3 screening in the third. Biallelic variants were found in NPR3 in all affected individuals. In one family 2 affected individuals were compound heterozygous for a missense and nonsense variant. The other two individuals were homozygous for missense and frameshift variants. The variants segregated with the phenotype in all 3 families. All variants were either not reported or appear at low frequency in dbSNP, ExAC and gnomAD databases and never in the homozyous state. Functional studies show that 3 of the variants either result in NMD or absent localization at the plasma membrane.
PMID: 10468599 Jaubert 1999 - analysis of mouse strains that have elongated bodies show that in each have mutations in the Npr3 gene.Created: 21 Jan 2021, 4:41 p.m. | Last Modified: 21 Jan 2021, 4:41 p.m.
Panel Version: 2.73
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
4 individuals in 3 families reported with striking phenotypic similarity.
Functional evidence compelling.
Mouse model recapitulates phenotype (including skeletal features).
Sources: LiteratureCreated: 19 Feb 2020, 6:54 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Tall stature; arachnodactyly; extra epiphyses; aortic dilatation
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag for-review was removed from gene: NPR3.
Source Expert Review Green was added to NPR3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: npr3 has been classified as Amber List (Moderate Evidence).
Publications for gene: NPR3 were set to PMID: 30032985; 10468599
Tag for-review tag was added to gene: NPR3.
gene: NPR3 was added gene: NPR3 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: NPR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NPR3 were set to PMID: 30032985; 10468599 Phenotypes for gene: NPR3 were set to Tall stature; arachnodactyly; extra epiphyses; aortic dilatation Penetrance for gene: NPR3 were set to unknown Review for gene: NPR3 was set to GREEN gene: NPR3 was marked as current diagnostic