Point mutation C18R in pre-pro-PTH gene in brother and sister with hypoparathyroidism, Fahr’s syndrome and epilepsy

Abstract

Idiopathic hypoparathyreoidism may be sporadic or familial, and may occur as an isolated defect or as a component of a more widespread disorder, such as autoimmune polyglandular failure type 1 or various developmental abnormalities. Familial isolated hypoparathyreoidism (FIH) can result from several types of genetic alterations, including, mutations in the calcium-sensing receptor (CASR) gene, glial cells missing-2 (GCM-2), G protein a11 (GNA11), or in the PTH gene itself. X-linked recessive hypoparathyroidism, a rare congenital form of hypoparathyroidism has also been described. Here, we report a family, brother and sister, with hypoparathyroidism, Fahr’s syndrome and epilepsy diagnosed in early childhood. The genetic testing proved a rare, point mutation in the PTH gene (C18R) with autosomal dominant inheritance. This is the first reported family from North Macedonia with FIH due to mutation in the PTH gene.