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

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RESEARCH PRODUCT

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

Susanne Thiele Joachim Pohlenz Olaf Hiort Pia Hermanns Julia Winter

subject

Male musculoskeletal diseases Heterozygote medicine.medical_specialty Erythrocytes Foot Deformities Congenital Endocrinology Diabetes and Metabolism Mutation Missense Parathyroid hormone Gallstones Gene mutation Hyperphosphatemia Endocrinology Internal medicine Chromogranins GTP-Binding Protein alpha Subunits Gs GNAS complex locus Humans Medicine Missense mutation natural sciences Amino Acid Sequence Child Conserved Sequence Pseudohypoparathyroidism Base Sequence Sequence Homology Amino Acid biology business.industry DNA Exons Gallstones medicine.disease Pedigree Cholesterol Endocrinology Amino Acid Substitution Pseudohypoparathyroidism Pediatrics Perinatology and Child Health biology.protein business Hand Deformities Congenital Hormone

description

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 (Gsalpha). PHP Ia and Albright hereditary osteodystrophy (AHO) are caused by a reduced activity of the Gsalpha 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. Gsalpha activity was measured in erythrocyte membranes from the patient and the GNAS coding region of Gsalpha sequenced. Results Gsalpha 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.

year	journal	country	edition	language
2011-08-10	Journal of Pediatric Endocrinology and Metabolism

https://doi.org/10.1515/jpem.2011.172