Skeletal dysplasia

Gene: PRKAR1A

Green List (high evidence)

Acromelic dysplasias gp of SD - >3 cases. Variants also associated with Myxoma, intracardiac 255960;Pigmented nodular adrenocortical disease, primary, 1 610489; Carney complex type 1 160980. recurrent R368* variant only. Other variants in gene associated with other phenotypes.; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Acrodysostosis 1, with or without hormone resistance 101800

Mode of pathogenicity
Other - please provide details in the comments

I don't know

The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 30 Jan 2023, 2:18 p.m. | Last Modified: 30 Jan 2023, 2:31 p.m.

Panel Version: 3.5

Comment on mode of inheritance: No reports of biallelic cases found so recommendation is to change the mode of inheritance to monoallelic only after GMS review.

Created: 13 Apr 2022, 3:34 p.m. | Last Modified: 13 Apr 2022, 3:34 p.m.

Panel Version: 2.199

Looking at the mode of inheritance of this gene on the Skeletal dysplasia panel where it is Both mono and bi-allelic.

In OMIM and Gene2Phenotype the relevant phenotypes of Acrodysostosis 1, with or without hormone resistance, OMIM:101800 and ACRODYSOSTOSIS respectively are listed with autosomal dominant/monoallelic inheritance.

There are several reports of heterozygous variants in PRKAR1A in patients with Acrodysostosis (PMIDs: 21651393, 22464250, 22464252, 28804209, 23425300, 25075981, 26763073). No reports of biallelic variants were found in a search of PubMed. Therefore the recommendation is for the mode of inheritance to be changed to monoallelic only.

Created: 13 Apr 2022, 3:31 p.m. | Last Modified: 13 Apr 2022, 3:31 p.m.

Panel Version: 2.195

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: PRKAR1A; Initial rating suggestion: green

Created: 6 Mar 2019, 11:36 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Acrodysostosis 1, with or without hormone resistance, OMIM:101800

Publications

• 21651393
• 22464250
• 22464252
• 28804209
• 23425300
• 25075981
• 26763073

Mode of pathogenicity
Other

Comment when marking as ready: Associated with phenotypes in G2P. Numerous variants reported in these phenotypes.

Created: 12 Jul 2016, 11:53 a.m.

Comment on phenotypes: Variants also reported in Carney complex, type 1 160980 and Adrenocortical tumor, somatic

Created: 12 Jul 2016, 11:52 a.m.

Green List (high evidence)

Tier 2

Created: 17 Jun 2016, 8:07 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Acrodysostosis 1, with or without hormone resistance 101800; Adrenocortical tumor, somatic; Carney complex, type 1 160980; Myxoma, intracardiac 255960; Pigmented nodular adrenocortical disease, primary, 1 610489

Variants in this GENE are reported as part of current diagnostic practice