Limb disorders
Gene: GNASThe mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 11:37 a.m. | Last Modified: 11 Oct 2023, 11:37 a.m.
Panel Version: 4.11
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Comment on mode of inheritance: For the phenotype pseudohypoparathyroidism, monoallelic and imprinted is the appropriate mode of inheritance as indicated. For the phenotype of McCune Albright syndrome, which includes polyostotic fibrous dysplasia, the mechanism is a post-zygotic variant leading to a somatic mosaic picture. The mode of inheritance is therefore still best matched to monoallelic, however depending on the level of mosaicism in the tissue tested, the proportion of alleles with the variant could vary considerably (from 0-50%) and therefore the ability to detect it.Created: 11 Jul 2017, 4:16 p.m.
Disease causing variants in the GNAS locus have differing expression panels. Pseudohypothyroidism Ia, Ib & Ic are all caused by GNAS variants arising in the maternal alleles, therefore, the mode of inheritance (MOI) for GNAS in these conditions should be monoallelic maternally imprinted. Pseudopseudohypoparathyroidism, OMIM:612463 and Osseous heteroplasia, progressive, OMIM:166350 are associated with variants in the paternal alleles therefore, the mode of inheritance for GNAS in these conditions should be monoallelic paternally imprinted. Because the Limb disorders panel is encompassing various phenotypes, the MOI should been set to monoallelic, imprinted status unknown.Created: 13 Oct 2022, 2:41 p.m. | Last Modified: 13 Oct 2022, 2:41 p.m.
Panel Version: 2.83
Listed as associated with Skeletal Dysplasia by Gene Advisor (June 2016), Steve AbbsCreated: 27 Jul 2016, 9:36 a.m.
Comment on mode of inheritance: All monogenic except for ACTH-independent macronodular adrenal hyperplasia 219080 (isolated cases) & McCune-Albright syndrome, 174800 (somatic mosaic)Created: 7 Jul 2016, 11:13 a.m.
Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)Created: 21 Jun 2016, 12:49 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Tier 1Created: 17 Jun 2016, 8:04 a.m.
Mode of inheritance
Other - please specify in evaluation comments
Phenotypes
ACTH-independent macronodular adrenal hyperplasia 219080 IC ; McCune-Albright syndrome, somatic, mosaic 174800 ; Osseous heteroplasia, progressive 166350; Pseudohypoparathyroidism Ia 103580; Pseudohypoparathyroidism Ib 603233; Pseudohypoparathyroidism Ic 612462; Pseudopseudohypoparathyroidism 612463
Variants in this GENE are reported as part of current diagnostic practice
Tag Q4_22_MOI was removed from gene: GNAS.
Source NHS GMS was added to GNAS. Mode of inheritance for gene GNAS was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Tag mosaicism tag was added to gene: GNAS. Tag Q4_22_MOI tag was added to gene: GNAS.
Phenotypes for gene: GNAS were changed from ACTH-independent macronodular adrenal hyperplasia 219080 IC; McCune-Albright syndrome, somatic, mosaic 174800; Osseous heteroplasia, progressive 166350; Pseudohypoparathyroidism Ia 103580; Pseudohypoparathyroidism Ib 603233; Pseudohypoparathyroidism Ic 612462; Pseudopseudohypoparathyroidism 612463 to Pseudohypoparathyroidism Ia, OMIM:103580; pseudohypoparathyroidism type 1A, MONDO:0007078; Pseudohypoparathyroidism Ib, OMIM:603233; pseudohypoparathyroidism type 1B, MONDO:0011301; Pseudohypoparathyroidism Ic, OMIM:612462; pseudohypoparathyroidism type 1C, MONDO:0012911; McCune-Albright syndrome, somatic, mosaic, OMIM:174800; panostotic fibrous dysplasia, MONDO:0043168; Osseous heteroplasia, progressive, OMIM:166350; ACTH-independent macronodular adrenal hyperplasia. OMIM:219080; ACTH-independent macronodular adrenal hyperplasia 1, MONDO:0020735; Pseudopseudohypoparathyroidism, OMIM:612463; pseudopseudohypoparathyroidism, MONDO:0012912
Ana Beleza: Tier 1
Expert Review Green was added to GNAS. Panel: Limb disorders Emory Genetics Laboratory was added to GNAS. Panel: Limb disorders Model of inheritance for gene GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
London South East RGC GSTT was added to GNAS. Panel: Limb disorders
GNAS was added to Limb disorders panel. Sources: Viapath
GNAS was created by Ellen McDonagh