In addition, it has been reported that the biallelically expressed upstream STX16 gene consists of cis-acting regulatory element for the GNAS locus, such that maternally inherited microdeletion in around exon 4 of the STX16 gene led to a loss of methylation at the Exon1A DMR (approx. 220 kb downstream of the STX16 exon 4) and biallelical Exon1A expression which are associated with autosomal-dominant PHP type Ib (AD-PHP1B) [19,20]. Here, GNAS is linked to Alzheimer disease.