Pseudohypoparathyroidism type Ia: a novel GNAS mutation in a Brazilian boy presenting with an early primary hypothyroidism

Abstract

Pseudohypoparathyroidism type Ia (PHP Ia) is a rare disease characterized by an elevated parathyroid hormone due to the resistance to its action in target tissues. We report a new GNAS mutation causing PHP Ia and an atypical early-onset primary hypothyroidism. A 3-year-old boy was diagnosed with obesity, delayed pyschomotor development, and round face. The laboratory evaluation at the age of 1 year showed primary hypothyroidism, hypocalcemia, hyperphosphatemia, elevated alkaline phosphatase, and parathyroid hormone. These data led to the diagnosis of PHP Ia. Molecular analysis revealed a novel missense mutation in GNAS exon 1 (TCG→CGC, Cys3→Arg) in both the child and his mother. Although previously reported cases described delayed subclinical hypothyroidism as the more common thyroid abnormality, we report a not previously described GNAS mutation associated with an atypical early-onset primary hypothyroidism. These observations broaden the clinical spectrum of PHP Ia and its associated mutations.

GNAS1 mutation analysis in gastrointestinal tumors

“…As a vital parameter in cellular signaling Gsa is ubiquitously found [7]. Different diseases are described with gain-of-function and loss-of-function mutations such as McCune-Albright-Syndrome, a disease which combines café-au-lait spots, polyostotic fibrous dysplasia and endocrinopathies [8], fibrous dysplasia itself [9] or endocrinological diseases like pseudohypoparathyroidism [10] with various mutation hotspots [11]. How imprinting mechanism of this gene leads to different diseases partly depending on parent's gender, is not totally understood [5].…”