Identification of a Novel Mutation in a Family with Pseudohypoparathyroidism Type 1a

Abstract

Introduction Pseudohypoparathyroidism type 1a is caused by GNAS mutations leading to target organ resistance to multiple hormones rather than parathyroid hormone, resulting not only in hypocalcemia, but also in Albright's hereditary osteodystrophy phenotype. Materials and Methods DNA sequencing of the GNAS gene identified a novel heterozygous mutation in peripheral blood leukocytes in the family presented in this case report. Results We present a case of a 25-year-old woman with pseudohypoparathyroidism type 1a admitted with seizures, whose family presents an autosomal dominant transmission of a novel heterozygous GNAS mutation (c.524_530+3del). Conclusion Pseudohypoparathyroidism type 1a is mostly caused by inactivating GNAS mutations that have been gradually reported in the literature that lead to a typical and complex clinical phenotype and resistance to multiple hormones. The deletion caused by the mutation identified in the presented case has not been reported previously.

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

“…7 The phenotype is most likely explained by the fact that some tissues (thyroid, pituitary, renal proximal tubules, and gonads) express Gsα predominantly from the maternal allele, while the paternal is silenced through yet unknown mechanisms. 13 In this case, a novel heterozygous frameshift mutation, NM_000516 (GNAS): c.860_861del p.(Val287Aspfs*12), in exon 11 of the GNAS gene was identified for PHP-1a diagnosis. This very rare variant (absent GnomAD) was also detected in the brother, the sister, and the mother, thus confirming its maternal transmission in the autosomal dominant mode.…”