PHPIB results from resistance to parathyroid hormone (PTH) in the renal proximal tubules leading to hypocalcaemia
and hyperphosphataemia and increased PTH in the serum. PHPIB is caused by defects at the GNAS locus (Tafaj O & Jüppner H 2016).
GNAS is located at 20q13 and contains 13 exons. GNAS codes for the alpha-subunit of stimulatory guanine-binding
nucleotide (Gsα) and 5 different mRNAs.
More than 60% of PHPIB cases are caused by defects at GNAS DMRs. 10-25% of cases are due to paternal UPD of
chromosome 20 and in rare cases the condition is due to deletions at the 20q13 locus (Soellner L et al 2017).