Congenital hypothyroidismGene: GNAS
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.
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.
This gene has been classified as Green List (High Evidence).
Mode of inheritance for GNAS was changed to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Phenotypes for GNAS were set to Pseudohypoparathyroidism Ia, 103580 (Hypothyroidism)
Model of inheritance for gene GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Phenotypes for gene GNAS were set to Pseudohypoparathyroidism Ia, 103580 (Hypothyroidism)
GNAS was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Eligibility statement prior genetic testing
GNAS was created by rfoulger