Abstract

Background Pseudohypoparathyroidism (PHP) is a rare disorder characterized by hypocalcemia, hyperphosphatemia, and resistance to parathyroid hormone (PTH). According to different GNAS mutations, PHP is divided into several subtypes, among which autosomal-dominant PHP1B (AD-PHP1B) is caused by STX16 deletion and epigenetic alteration of GNAS . Although the deletion of STX16 exons 2−6 is commonly observed, other mutations involving STX16 can also result in AD-PHP1B. Materials and methods The clinical information of a 38-year-old male PHP patient was collected. The genomic DNA from peripheral blood cells was extracted for genetic analysis of GNAS and upstream STX16 by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and whole-exome sequencing (WES). Sanger sequencing was performed to verify the break point of the novel long-range deletion. Results The patient’s medical history of tetany and seizure as well as laboratory examination showing hypocalcemia and elevated PTH levels indicated the diagnosis of PHP. The results of MS-MLPA showed loss of methylation of GNAS A/B :TSS-DMR and half-reduced copy number of STX16 exon 1−9, which revealed the subtype of AD-PHP1B. Furthermore, the WES study displayed a 87.5 kb missing upstream of GNAS . A 87.5 kb deletion spanning STX16 and NPEPL1 together with an insertion of 28 bp of unknown origin was verified by PCR along with Sanger sequencing. Conclusions A novel deletion of 87.5 kb spanning STX16 and NPEPL1 was discovered in an AD-PHP1B patient, which provides new information on molecular defects leading to AD-PHP1B.