title: Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance.
abstract: The skeletal dysplasia characteristic of acrodysostosis resembles the Albright's hereditary osteodystrophy seen in patients with pseudohypoparathyroidism type 1a, but defects in the α-stimulatory subunit of the G-protein (GNAS), the cause of pseudohypoparathyroidism type 1a, are not present in patients with acrodysostosis. We report a germ-line mutation in the gene encoding PRKAR1A, the cyclic AMP (cAMP)-dependent regulatory subunit of protein kinase A, in three unrelated patients with acrodysostosis and resistance to multiple hormones. The mutated subunit impairs the protein kinase A response to stimulation by cAMP; this explains our patients' hormone resistance and the similarities of their skeletal abnormalities with those observed in patients with pseudohypoparathyroidism type 1a.
authors.affiliation: INSERM Unité 986, Hôpital St. Vincent de Paul, Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Linglart
authors.forename: Christine
authors.initials: C
authors.lastname: Menguy
authors.forename: Alain
authors.initials: A
authors.lastname: Couvineau
authors.forename: Colette
authors.initials: C
authors.lastname: Auzan
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Gunes
authors.forename: Mathilde
authors.initials: M
authors.lastname: Cancel
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Motte
authors.forename: Graziella
authors.initials: G
authors.lastname: Pinto
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
authors.forename: Eric
authors.initials: E
authors.lastname: Clauser
authors.forename: Caroline
authors.initials: C
authors.lastname: Silve
mesh_terms: D000293:Adolescent; D002648:Child; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004351:Drug Resistance; D004413:Dysostoses / Q000235:genetics / Q000378:metabolism; D005260:Female; D018095:Germ-Line Mutation; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism; D008297:Male; D010009:Osteochondrodysplasias / Q000235:genetics / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010375:Pedigree; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D006728:Hormones; C517834:PRKAR1A protein, human; D010281:Parathyroid Hormone; D017868:Cyclic AMP-Dependent Protein Kinases