A novel GNAS mutation in pseudohypoparathyroidism type 1a in a Chinese man presented with recurrent seizure: a case report

Abstract

Background Pseudohypoparathyroidism is a rare genetic disease characterized by hypocalcaemia and hyperphosphataemia due to the defect to the guanine nucleotide-binding protein alpha subunit (GNAS) gene. Patients with pseudoparathyroidism type 1a and 1c could manifest Albright’s hereditary osteodystrophy and multiple hormone resistance including gonadotropin and thyroid stimulating hormone. Case presentation Here we report a Chinese man who presented with fatigue, recurrent seizure and Albright’s hereditary osteodystrophy. His genetic study revealed a heterozygote mutation in the GNAS gene [NM_000516.4(GNAS): c2787_2788del (p.Val930AspfsTer12)]. After calcium and calcitriol supplement, his seizures achieved partially remission. Conclusions We report a case of PHP1a or 1c with a novel frameshift mutation in GNAS gene in a patient presenting with AHO, as well as TSH and partial gonadotropin resistance. This mutation in this case has not been reported in literature and adds to the spectrum of genetic mutations related to PHP.

New insights into thyroid dysfunction in patients with inactivating parathyroid hormone/parathyroid hormone-related protein signalling disorder (the hormonal and ultrasound aspects): One-centre preliminary results

“…Studies on thyroid imaging in iPPSD are insufficient (7,(23)(24)(25). Elli et al found normal thyroid scans in a cohort of patients (7).…”

“…There are few reports of thyroid ultrasound evaluation in iPPSD (7,(23)(24)(25). From a clinical paediatric endocrine standpoint, it is interesting and of practical value to determine how TSH resistance extrapolates to the ultrasound structure of the thyroid gland.…”

Fahr syndrome discovered in adulthood revealing a rare GNAS mutation in pseudohypoparathyroidism type 1a in a Tunisian family

“…Several variants of PHP have been identified. The molecular defects in the GNAS gene encoding the alpha subunit of the stimulatory G protein (Gs α ) contribute to at least 3 different forms of the disease: PHP type 1a, PHP type 1b, and pseudopseudohypoparathyroidism 3 …”

“…PHP‐1 is further divided into three different subtypes: 1a, 1b, and 1c 3 . PHP‐1c, which is identical to PHP‐1a in terms of the presence of AHO and hormone resistance, but in contrast to PHP‐1a, in vitro assessment of Gs‐alpha protein activity, reveals no abnormality, and mutations of GNAS are usually not observed 4 …”

“…The molecular defects in the GNAS gene encoding the alpha subunit of the stimulatory G protein (Gsα) contribute to at least 3 different forms of the disease: PHP type 1a, PHP type 1b, and pseudopseudohypoparathyroidism. 3 PHP-1 is further divided into three different subtypes: 1a, 1b, and 1c. 3 PHP-1c, which is identical to PHP-1a in terms of the presence of AHO and hormone resistance, but in contrast to PHP-1a, in vitro assessment of Gs-alpha protein activity, reveals no abnormality, and mutations of GNAS are usually not observed.…”