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Gs Transcripts Are Biallelically Expressed in the Human Kidney Cortex: Implications for Pseudohypoparathyroidism Type 1b

Departments of Pediatrics (H.Z., G.N.H., C.G.G.), Medicine (J.A.M., G.N.H., C.G.G.), Human Genetics (G.N.H.), and Physiology (G.R., G.N.H.), McGill University, Montréal, Québec, Canada H3Z 2Z3

Address all correspondence and requests for reprints to: Cynthia G. Goodyer, Ph.D., Endocrine Research Laboratory, 4th Floor, Place Toulon, Room 415/1, McGill University–Montreal Children’s Hospital Research Institute, 4060 Ste. Catherine Street W., Westmount, Québec, Canada H3Z 2Z3. E-mail: cindy.goodyer{at}muhc.mcgill.ca

Abstract

Pseudohypoparathyroid type 1b patients are characterized by renal resistance to PTH in the absence of Albright’s hereditary osteodystrophy or other endocrine abnormalities. Kindred studies have suggested that the cause of this resistance is a specific decrease in Gs activity in renal proximal tubules due to paternal imprinting of Gs. To test this, allelic expression of Gs was analyzed in human fetal kidney cortex samples by RT-PCR assays. The results showed that, in contrast to the parent-specific expression of exon 1A and XLs (paternal) or NESP (maternal) mRNAs, Gs transcripts are biallelically expressed in human kidney cortex. These data implicate abnormal imprinting of alternative regions within the GNAS1 locus as a more likely cause of pseudohypoparathyroid type 1b.

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