De Novo STX16 Deletions: An Infrequent Cause of Pseudohypoparathyroidism Type Ib that Should Be Excluded in Sporadic Cases

Context: Maternally inherited 3-kb STX16 deletions cause autosomal dominant pseudohypoparathyroidism type Ib (PHP-Ib) characterized by PTH resistance with loss of methylation restricted to the GNAS exon A/B. Objective: The objective of the study was to search for the 3-kb STX16 deletion and to establish haplotypes for the GNAS region for two PHP-Ib patients and their families. Setting: The study was conducted at a research laboratory and tertiary care hospitals. Patients: The index cases presented at the ages 8 and 9.5 yr, respectively, with hypocalcemia, hyperphosphatemia, and elevated PTH. Interventions: There were no interventions. Results: DNA analyses of the index cases revealed an isolated loss of the GNAS exon A/B methylation and the 3-kb STX16 deletion. In the first family, the patient's healthy mother and sister showed no genetic or epigenetic abnormality, yet microsatellite analysis of the GNAS region indicated that both siblings share the same maternal allele, with the exception of an allelic l...