Monogenic short stature

Gene: NPR2

The rating of this gene has been updated to GREEN and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 31 Jan 2023, 5:28 p.m. | Last Modified: 31 Jan 2023, 5:28 p.m.

Panel Version: 2.33

Comment on list classification: There is sufficient evidence to rate this gene as Green under a biallelic MOI - causes severe dwarfism that is usually diagnosed at birth and becomes more obvious in the first 2 years of life (MIM# 602875). Monoallelic variants can cause idiopathic short stature (MIM# 616255) however the associated height and age at which short stature becomes apparent does not meet the criteria of the panel (height ≤−3 SDS at the age of at least 2 years).

Created: 5 Jan 2023, 5:14 p.m. | Last Modified: 5 Jan 2023, 5:14 p.m.

Panel Version: 2.13

Review submitted on behalf of Helen Storr. Mode of inheritance: AR and AD. Phenotypes: Alteration of the NPR2 signaling cascade leads to growth disorders; downregulation leads to short stature, and upregulation leads to excessive growth. Biallelic defects lead to severe skeletal dysplasia (acromesomelic dysplasia, Maroteaux type) and heterozygous NPR2 variants cause short stature with possible presence of different signs of bone dysplasia. Publications: Well established. Severe Maroteaux type skeletal dysplasia described in 2003. Heterozgous defects assocuated with short stature from 2013 onwards. . Mechansim: The C-type natriuretic peptide receptor encoded by the NPR2 gene is a paracrine regulator of the growth plate. Penetrance: Full penetrance.

Created: 22 Dec 2022, 11:07 a.m. | Last Modified: 22 Dec 2022, 11:07 a.m.

Panel Version: 2.5

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal