Skeletal dysplasia
Gene: GNAS
Acromelic dysplasias gp of SD, disorganized development of skeletal components gp of SD. Several cases. Also mutated in ACTH-independent macronodular adrenal hyperplasia 219080 IC;Pseudohypoparathyroidism Ic 612462;Pseudopseudohypoparathyroidism 612463; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Phenotypes
McCune-Albright syndrome, somatic, mosaic 174800; Osseous heteroplasia, progressive 166350; Pseudohypoparathyroidism Ia 103580; Pseudohypoparathyroidism Ib 603233
The 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, 11:08 a.m. | Last Modified: 11 Oct 2023, 11:08 a.m.
Panel Version: 4.20
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: GNAS; Initial rating suggestion: greenCreated: 6 Mar 2019, 11:36 a.m.
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 Skeletal dysplasia panel is representing various phenotypes, the MOI has been set to monoallelic, imprinted status unknown.Created: 13 Oct 2022, 5:42 p.m. | Last Modified: 13 Oct 2022, 5:42 p.m.
Panel Version: 2.222
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.
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 Q4_22_MOI tag was added to gene: GNAS.
Phenotypes for gene: GNAS were changed from Pseudohypoparathyroidism Ia 103580; Pseudopseudohypoparathyroidism 612463; Osseous heteroplasia, progressive 166350; Pseudohypoparathyroidism Ib 603233; Pseudohypoparathyroidism Ic 612462; ACTH-independent macronodular adrenal hyperplasia 219080 IC; McCune-Albright syndrome, somatic, mosaic 174800 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
Added phenotypes Pseudohypoparathyroidism Ia 103580; Pseudohypoparathyroidism Ib 603233; Osseous heteroplasia, progressive 166350; McCune-Albright syndrome, somatic, mosaic 174800 for gene: GNAS
Source NHS GMS was added to GNAS. Rating Changed from Green List (high evidence) to Green List (high evidence)
Mode of inheritance for GNAS was changed to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Promoted to version 1 9th August 2016
Mode of inheritance for GNAS was changed to Other - please specifiy in evaluation comments
Phenotypes for GNAS were set to 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
This gene has been classified as Green List (High Evidence).
GNAS was added to Unexplained skeletal dysplasiapanel. Source: Emory Genetics Laboratory GNAS was added to Unexplained skeletal dysplasiapanel. Source: Expert Review Red
GNAS was added to Unexplained skeletal dysplasiapanel. Sources:
GNAS was created by sleigh