Skeletal dysplasia
Gene: PRKG2The 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
We recently reported details of 4 individuals from two independent families with homozygous frameshift/stop-gains in this gene segregating with a variable skeletal condition comprising spondylometaphyseal/acromesomelic dysplasia (PMID: 34782440). This helps to confirm an earlier report of this gene-disease association in two small families (PMID: 33106379). In addition to the rodent and bovine models, there is also a dog model for this genetic condition now (PMID: 34680883).Created: 17 Nov 2021, 9:40 a.m. | Last Modified: 17 Nov 2021, 9:40 a.m.
Panel Version: 2.154
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
spondylometaphyseal; acromesomelic dysplasia
Publications
Comment on phenotypes: Added relevant phenotypes now listed in OMIM (MIM# 619636 and MIM# 619638)Created: 4 Jan 2022, 12:15 p.m. | Last Modified: 4 Jan 2022, 12:15 p.m.
Panel Version: 2.163
Comment on list classification: Rating Amber but should be promoted to Green at the next GMS panel update (added 'for-review tag). Two unrelated cases exhibiting a consistent phenotype, supported by functional characterisation of harboured variants and concordant animal models.Created: 2 Nov 2020, 1:26 p.m. | Last Modified: 2 Nov 2020, 1:26 p.m.
Panel Version: 2.26
- PMID: 33106379 (2020) - Distinct homozygous variants in PRKG2 identified in two unrelated individuals, both with a skeletal dysplasia associated with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones.
Functional studies showed both variants result in NMD and disrupt the downstream MAPK signalling pathway in response to FGF2. The role of cGKII, encoded by PRKG2, in skeletal growth has been established in several animal models (references provided in paper).
Sources: LiteratureCreated: 2 Nov 2020, 1:13 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Acromesomelic dysplasia
Publications
Tag Q4_21_NHS_review was removed from gene: PRKG2.
Tag for-review was removed from gene: PRKG2.
Source Expert Review Green was added to PRKG2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: PRKG2 were changed from acromesomelic dysplasia, MONDO:0019696; spondylometaphyseal dysplasia, MONDO:0016763 to Acromesomelic dysplasia 4, OMIM:619636; Spondylometaphyseal dysplasia, Pagnamenta type, OMIM:619638
Tag Q4_21_NHS_review tag was added to gene: PRKG2.
Phenotypes for gene: PRKG2 were changed from Acromesomelic dysplasia to acromesomelic dysplasia, MONDO:0019696; spondylometaphyseal dysplasia, MONDO:0016763
Publications for gene: PRKG2 were set to 33106379
Gene: prkg2 has been classified as Amber List (Moderate Evidence).
Tag watchlist was removed from gene: PRKG2. Tag for-review tag was added to gene: PRKG2.
gene: PRKG2 was added gene: PRKG2 was added to Skeletal dysplasia. Sources: Literature watchlist tags were added to gene: PRKG2. Mode of inheritance for gene: PRKG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRKG2 were set to 33106379 Phenotypes for gene: PRKG2 were set to Acromesomelic dysplasia Review for gene: PRKG2 was set to AMBER