Skeletal dysplasia
Gene: PRKAR1A
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 LesterCreated: 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
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: greenCreated: 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
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, somaticCreated: 12 Jul 2016, 11:52 a.m.
Tier 2Created: 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
Tag Q2_22_MOI was removed from gene: PRKAR1A.
Mode of inheritance for gene PRKAR1A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of inheritance for gene: PRKAR1A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PRKAR1A were changed from Acrodysostosis 1, with or without hormone resistance 101800; Myxoma, intracardiac 255960; Pigmented nodular adrenocortical disease, primary, 1 610489 to Acrodysostosis 1, with or without hormone resistance, OMIM:101800
Publications for gene: PRKAR1A were set to
Mode of pathogenicity for gene: PRKAR1A was changed from to Other
Tag Q2_22_MOI tag was added to gene: PRKAR1A.
Added phenotypes Acrodysostosis 1, with or without hormone resistance 101800 for gene: PRKAR1A
Source NHS GMS was added to PRKAR1A. Rating Changed from Green List (high evidence) to Green List (high evidence)
Promoted to version 1 9th August 2016
This gene has been classified as Green List (High Evidence).
Phenotypes for PRKAR1A were set to Acrodysostosis 1, with or without hormone resistance 101800; Myxoma, intracardiac 255960; Pigmented nodular adrenocortical disease, primary, 1 610489
Mode of inheritance for PRKAR1A was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
PRKAR1A was added to Unexplained skeletal dysplasiapanel. Sources: Emory Genetics Laboratory,Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN
PRKAR1A was created by sleigh
PRKAR1A was added to Unexplained skeletal dysplasiapanel. Sources: