Pathogenic variants of the <i>GNAS</i> gene introduce an abnormal amino acid sequence in the β6 strand/α5 helix of Gsα, causing pseudohypoparathyroidism type 1A and pseudopseudohypoparathyroidism in two unrelated Japanese families.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36407415.
- Also identified by DOI 10.1016/j.bonr.2022.101637 and PMC identifier 9668531.
- Licence recorded as CC BY.
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Abstract
Pseudohypoparathyroidism 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP) are caused by loss-of-function variants of <i>GNAS</i>, which encodes Gsα. We present two unrelated Japanese families with PHP1A and PPHP harboring unreported pathogenic variants of <i>GNAS</i> (c.1141delG, p.Asp381Thrfs*23 and c.1117delC, p.Arg373Alafs*31). These variants introduce abnormal amino acids in the β6 strand/α5 helix of Gsα, which interact with G protein coupling receptor (GPCR). We conclude that these variants alter the association of Gsα with GPCR and cause PHP1A or PPHP.