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Madelung-like deformity in pseudohypoparathyroidism type 1b
Janine Sanchez1, Erasmo Perera, Suzanne Jan de Beur
1Division of Pediatric Endocrinology, MCCD 3044A, D820, 1601 NW 12th Avenue, Miami, Florida 33136. jsanchez@med.miami.edu.
The Journal of Clinical Endocrinology and Metabolism
|July 15, 2011
Summary
Pseudohypoparathyroidism type 1b (PHP 1b) can cause growth plate defects like brachydactyly. This study links PHP 1b to GNAS imprinting defects, suggesting GNAS signaling is crucial for chondrocyte maturation.
Area of Science:
- Endocrinology
- Genetics
- Skeletal Biology
Background:
- Pseudohypoparathyroidism (PHP) types 1a and 1b are distinct genetic disorders.
- PHP 1b is characterized by resistance to parathyroid hormone (PTH).
- This study investigates an extended family with PHP 1b exhibiting unusual growth plate abnormalities.
Purpose of the Study:
- To characterize clinical, biochemical, and molecular features of PHP 1b in an extended kindred.
- To investigate the genetic basis of associated growth plate defects.
- To explore the role of GNAS imprinting in chondrocyte maturation.
Main Methods:
- Clinical examinations and assessment of mineral metabolism and thyroid function.
- Skeletal radiography to evaluate bone abnormalities.
- Genetic analysis of GNAS and STX16 genes, including linkage and methylation studies.
Main Results:
- 23 out of 37 family members had PHP 1b.
- Ten affected individuals presented with brachydactyly E, including two with Madelung-like deformities.
- Genetic analysis revealed a 3.0-kb deletion in the STX16 gene and loss of maternal epigenotype in GNAS exon 1A.
Conclusions:
- An imprinting defect in GNAS is associated with PHP 1b and growth plate abnormalities.
- Brachydactyly and Madelung deformity can be manifestations of GNAS imprinting defects.
- GNAS signaling is critical for normal chondrocyte maturation and skeletal development.
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