Danzig J, Li D, de Beur SL, et al. - Researchers sought to characterize epigenetic and genetic defects in patients with pseudohypoparathyroidism type 1b (PHP1b). Quantitative pyrosequencing of GNAS differentially methylated regions (DMRs), microarray analysis, and microsatellite haplotype analysis were performed on DNA from 84 individuals, including 26 individuals with sporadic PHP1b, 27 affected individuals and 17 unaffected and/or obligate gene carriers from 12 PHP1b families, 11 healthy individuals, and 3 individuals with PHP1a. Loss of methylation (LOM) at the exon A/B DMR was identified in all PHP1b individuals. LOM was identified only at the exon A/B DMR among the affected members of nine PHP1b kindreds, which was linked with a 3-kb deletion of STX16 exons 4-6 in seven families and a novel deletion of STX16 and adjacent NEPEPL1 in one family. They identified a novel NESP deletion in one of two other families with more extensive methylation defects. One sporadic PHP1b had UPD of 20q, two had 3-kb STX16 deletions, and five had apparent epigenetic mosaicism. The findings overall suggest diverse patterns of defective methylation and revealed novel or previously known mutations in 9 of 12 PHP1b families.