Novel mutations in the vitamin D receptor gene causing hereditary vitamin D-resistant rickets type 2A in two Indian families

ABSTRACT Hereditary vitamin D-resistant rickets type 2A (HVDRR2A; OMIM 277440) is caused by heterogeneous mutations in the vitamin D receptor (VDR) gene and is transmitted as an autosomal recessive trait. In this study, we report the clinical profile and management of two Indian cases of HVDRR2A, both presenting with alopecia and bony deformities. Blood investigations revealed hypocalcemia, elevated intact parathyroid hormone (iPTH), and high levels of 1,25-dihydroxyvitamin D [1,25(OH)2D3]. Molecular studies identified a novel homozygous c.1090 C > T (p.Gln364Ter) pathogenic variant in the VDR gene, resulting in a stop codon and premature protein truncation at the 364th amino acid position. Both patients were managed with intravenous calcium, high oral calcitriol, and cholecalciferol sachets.