Analysis of GNAS1 and overlapping transcripts identifies the parental origin of mutations in patients with sporadic Albright hereditary osteodystrophy and reveals a model system in which to observe the effects of splicing mutations on translated and untranslated messenger RNA.

ABSTRACT: Albright hereditary osteodystrophy (AHO) is caused by heterozygous deactivating GNAS1 mutations. There is a parent-of-origin effect. Maternally derived mutations are usually associated with resistance to parathyroid hormone termed "pseudohypoparathyroidism type Ia." Paternally derived mutations are associated with AHO but usually normal hormone responsiveness, known as "pseudo-pseudohypoparathyroidism." These observations can be explained by tissue-specific GNAS1 imprinting. Regulation of the genomic region that encompasses GNAS1 is complex. At least three upstream exons that splice to exon 2 of GNAS1 and that are imprinted have been reported. NESP55 is exclusively maternally expressed, whereas exon 1A and XL alphas are exclusively paternally expressed. We set out to identify the parental

SUBMITTER: Rickard SJ 

PROVIDER: S-EPMC1180358 | biostudies-literature | 2003 Apr

REPOSITORIES: biostudies-literature