Congenital hypothyroidism

Gene: GNAS

Green List (high evidence)

GNAS (GNAS complex locus)
EnsemblGeneIds (GRCh38): ENSG00000087460
EnsemblGeneIds (GRCh37): ENSG00000087460
OMIM: 139320, Gene2Phenotype
GNAS is in 19 panels

1 review

Rebecca Foulger (Genomics England curator)

PMID: 23412865 (Alvest et al., 2013) identify a GNAS mutation in Brazilian boy presenting with primary hypothyroidism and a diagnosis of pseudohypoparathyroidism-Ia. Molecular analysis revealed a novel missense mutation in GNAS exon 1 (TCG→CGC, C3R) in both the child and his (affected?) mother.
Created: 14 Feb 2017, 5:39 p.m.
Comment on list classification: Updated rating from Red to Green: Recommended for prior genetic testing plus >3 cases linked to MIM:103580, which presents with hypothyroidism.
Created: 14 Feb 2017, 5:38 p.m.
Romanet et al., 2015 (PMID:25802348) report a case of Pseudohypoparathyroidism (PHP) caused by epigenetic (methylation) changes in GNAS in a patient with congenital hypothyroidism.
Created: 14 Feb 2017, 3:23 p.m.
Comment on mode of inheritance: On GeCIP imprinting list.
Created: 13 Feb 2017, 3:21 p.m.
PMID:27922245 (Kirel et al., 2016) report a heterozygous mutation in the GNAS gene (IVS4+5G>C) in two related patients: a boy wtih PHP type Ia and his mother with pseudoPHP. The boy was first diagnosed as having primary hypothyroidism at 2.5 months.
Created: 13 Feb 2017, 3:18 p.m.
PMC:3961212 (Wu et al. 2014) studied 7 patients from 5 families including 6 patients with PHP1A. 5 of the PHP1A patients had primary hypothyroidism with elevated TSH levels. They report 5 new GNAS mutations across 5 families: c.85C>T (p.Q29*), c.103C>T (p.Q35*), c.840-2A>G (p.R280Sfs*21), c.1027_1028delGA (p.D343*), and c.1174G>A (p.E392K).
Created: 13 Feb 2017, 3:13 p.m.
In a 10-year-old Caucasian girl with brachymetacarpia, mental retardation, normocalcemic pseudohypoparathyroidism, and hypothyroidism (MIM:103580), Thiele et al.2007 (PMID:17299070) identified a heterozygous insertion of an adenosine in exon 3 of the GNAS gene.
Created: 13 Feb 2017, 3:02 p.m.
Comment on phenotypes: Hypothyroidism is a particular condition observed in pseudohypoparathyroidism (PHP), and congenital hypothryoidism can provide an early diagnostic clue for PHP1A (Source: PMID:25591844).
Created: 13 Feb 2017, 2:49 p.m.

History Filter Activity

22 Feb 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

22 February 2017: Promoted to Version 1. Reviews were assessed, and panel was revised according to expert review and additional curation. After discussion with the reviewer and in-house clinicians, it was agreed to include the genes for 'combined pituitary hormone deficiency' (CPHD) on the panel, since patients can present with central hypothyroidism (CH). In these cases, CH does not occur in isolation, but is one of the evolving pituitary hormone deficiencies.

14 Feb 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

13 Feb 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for GNAS was changed to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

13 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for GNAS were set to Pseudohypoparathyroidism Ia, 103580 (Hypothyroidism)

13 Feb 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Model of inheritance for gene GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

13 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene GNAS were set to Pseudohypoparathyroidism Ia, 103580 (Hypothyroidism)

23 Jan 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

GNAS was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Eligibility statement prior genetic testing

23 Jan 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

GNAS was created by rfoulger