Variable skeletal phenotypes associated with biallelic variants in PRKG2

The 100 000 Genomes Project (100KGP) is a UK-wide initiative that has a goal of using whole genome sequencing (WGS) to identify genetic causes of rare inherited diseases and embed the use of this technology within the NHS.1 Using data from this resource alongside international gene-matching efforts, four individuals from two independent families were identified harbouring homozygous frameshift or stop-gain variants in PRKG2, a recently described skeletal dysplasia gene.2 Detailed clinical and radiological assessments helped extend the phenotypic range associated with this autosomal recessive condition while functional studies indicated that both variants had a similar impact on FGF-induced MAPK signalling. PRKG2 encodes the cyclic guanosine monophosphate dependent protein kinase II (cGKII), which acts downstream of the natriuretic peptide receptor-B/C- natriuretic peptide (NPR-B/CNP). NPR-B is encoded by NPR2, biallelic variants in which are responsible for acromesomelic dysplasia, Maroteaux type (AMDM; MIM 602875). Rodent models further implicate PRKG2...

Source: Journal of Medical Genetics - September 26, 2022 Category: Genetics & Stem Cells Authors: Pagnamenta, A. T., Diaz-Gonzalez, F., Banos-Pinero, B., Ferla, M. P., Toosi, M. B., Calder, A. D., Karimiani, E. G., Doosti, M., Wainwright, A., Wordsworth, P., Bailey, K., Ejeskär, K., Lester, T., Maroofian, R., Heath, K. E., Tajsharghi, H., Shea Tags: Open access Genotype-phenotype correlations Source Type: research