Imprinting disorders

Gene: GNAS

Green List (high evidence)

GNAS is a complex imprinted locus that produces multiple transcripts through the use of alternative promoters and alternative splicing. The most well-characterized transcript derived from GNAS, Gs-alpha, encodes the alpha subunit of the stimulatory guanine nucleotide-binding protein (G protein). Gs-alpha is biallelically expressed except in a small number of tissues, including renal proximal tubules, thyroid, gonads, and pituitary, where it is predominantly expressed from the maternal GNAS allele.

Maternally inherited mutations lead to Albright hereditary osteodystrophy (AHO) plus PTH, TSH, and gonadotropin resistance (pseudohypoparathyroidism type 1A), whereas paternally inherited mutations lead to AHO alone. Pseudohypoparathyroidism type 1B, in which patients develop PTH resistance without AHO, is almost always associated with a GNAS imprinting defect in which both alleles have a paternal-specific imprinting pattern on both parental alleles.

Created: 17 Oct 2021, 5:50 a.m. | Last Modified: 17 Oct 2021, 5:50 a.m.

Panel Version: 0.19

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

Phenotypes
Pseudohypoparathyroidism Ia, MIM# 103580; Albright hereditary osteodystrophy; Pseudohypoparathyroidism Ib, MIM# 603233

Publications

• 15331575