A new heterozygous mutation (D196N) in the Gs alpha gene as a cause for pseudohypoparathyroidism type IA in a boy who had gallstones

作者：Winter Julia; Hiort Olaf; Hermanns Pia; Thiele Susanne; Pohlenz Joachim^*

来源：Journal of Pediatric Endocrinology & Metabolism, 2011, 24(5-6): 297-301.

DOI：10.1515/JPEM.2011.172

• children
• cholelithiasis
• Gs alpha (GNAS) gene
• mutation
• pseudohypoparathyroidism

Background: Pseudohypoparathyroidism (PHP) is characterized by hypocalcemia and hyperphosphatemia in association with an increased secretion of parathyroid hormone (PTH) due to decreased target tissue responsiveness to PTH. Patients with PHP type Ia are not only resistant to PTH, but also to other hormones that bind to receptors coupled to stimulatory G protein (Gs alpha). PHP Ia and Albright hereditary osteodystrophy (AHO) are caused by a reduced activity of the Gs alpha protein. Heterozygous inactivating Gs alpha (GNAS) gene mutations have been identified in these patients.
Methods: We studied a boy with PHP Ia. During follow-up the patient developed elevated liver enzyme serum levels and abdominal discomfort. Gs alpha activity was measured in erythrocyte membranes from the patient and the GNAS coding region of Gs alpha sequenced.
Results: Gs a activity was reduced (62 %) and molecular analysis revealed a new heterozygous GNAS gene mutation (D196N). Gallstones were diagnosed and cholecystectomy was performed. Biochemical analysis revealed cholesterol stones, a condition that was not reported before in PHP Ia.
Conclusions: Cholesterol gallstones may rarely be associated with PHP Ia and should be taken into account.

• 出版日期2011-6