Pathogenic variants of the GNAS gene introduce an abnormal amino acid sequence in the ß6 strand/α5 helix of Gsα, causing pseudohypoparathyroidism type 1A and pseudopseudohypoparathyroidism in two unrelated Japanese families.
Bone Rep
; 17: 101637, 2022 Dec.
Article
en En
| MEDLINE
| ID: mdl-36407415
ABSTRACT
Pseudohypoparathyroidism 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP) are caused by loss-of-function variants of GNAS, which encodes Gsα. We present two unrelated Japanese families with PHP1A and PPHP harboring unreported pathogenic variants of GNAS (c.1141delG, p.Asp381Thrfs*23 and c.1117delC, p.Arg373Alafs*31). These variants introduce abnormal amino acids in the ß6 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.
AHO, Albright's hereditary osteodystrophy; GNAS gene; GPCR, G protein coupling receptors;; Gsα; HGMD, Human Gene Mutation Database; IRB, Institutional review Board; NMD, Nonsense-mediated decay; Pseudohypoparathyroidism 1A (PHP1A); Pseudopseudohypoparathyroidism (PPHP); TSH, Thyroid-stimulating hormone; ß6 strand/α5 helix
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Bone Rep
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón