Imprinting disorders

Gene: STX16

Green List (high evidence)

Multiple reports of a PHP-Ib phenotype.

Caused in most cases by a maternally inherited 3-kb, 4.4-kb or larger deletion involving STX16, which is associated with loss of methylation (LOM) at GNAS exon A/B DMR (also referred to as exon 1A or GNAS A/B:TSS-DMR).

Of PHP1B cases, 15–20% are familial, with an autosomal dominant mode of inheritance (AD-PHP1B) through the maternal lineage. In this familial form, the methylation defect is usually limited to loss of methylation at GNAS A/B:TSS-DMR, secondary to a 3 kb microdeletion on the maternal allele of cis-acting control elements within STX16. Other maternally inherited deletions and duplications have also been identified in some rare familial cases affecting either an isolated GNAS A/B:TSS-DMR or all four DMRs (Nature review, PMID 29959430)

STX16 is not clearly an imprinted gene, but only maternally inherited deletions are associated with this phenotype. Deletions in this gene are thought to disrupt cis-acting regulation of GNAS expression.
Sources: Literature

Created: 20 Oct 2021, 9:11 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

Phenotypes
Pseudohypoparathyroidism type 1b MIM no: 603233

Publications

• PMID: 1456170
• 15579741
• 15800843
• 33320452
• 32337648
• 33247854
• 29959430