Journal
BONE
Volume 48, Issue 3, Pages 659-662Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2010.10.168
Keywords
Pseudohypoparathyroidism; Parathyroid hormone; Stimulatory G protein; GNAS; Imprinting
Categories
Funding
- National Institutes of Diabetes and Digestive and Kidney Disease [R01 DK073911, R37 DK46718]
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Pseudohypoparathyoridism type Ib (PHP-Ib) typically defines the presence of end-organ resistance to parathyroid hormone in the absence of Albright's hereditary osteodystrophy. Patients affected by this disorder present with imprinting defects in the complex GNAS locus. Microdeletions within STX16 or GNAS have been identified in familial cases with PHP-Ib, but the molecular cause of the GNAS imprinting defects in sporadic PHP-Ib cases remains poorly defined. We now report a case with sporadic PHP-Ib for whom a SNPlex analysis revealed loss of the maternal GNAS allele. Further analysis of the entire genome with a 100 K SNP chip identified a paternal uniparental isodisomy affecting the entire chromosome 20 without evidence for another chromosomal abnormality. Our findings explain the observed GNAS methylation changes and the patient's hormone resistance, and furthermore suggest that chromosome 20 harbors, besides GNAS, no additional imprinted region that contributes to the clinical and laboratory phenotype. (C) 2010 Elsevier Inc. All rights reserved.
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