ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
27148570 In Ye Y et al 2015, they had 7 patients with developmental delay and microcephaly, and de novo loss-of function mutations in POGZ were detected by whole-exome sequencing in 6 of the patients. Four of the patients had frameshift mutation, one patient had nonsense mutation, and another one had a heterozygous deletion of exons 4-19. All of these variants were predicted to cause loss of function.
26942287 In Stessman et al 2016, they collected clinical and molecular data of 25 individuals with disruptive mutations in POGZ by diagnostic whole-exome, whole-genome, or targeted sequencing of 5,223 patients with neurodevelopmental disorders (intellectual disability and autism spectrum disorders primarily). All of the variants were de novo, either frameshift or nonsense mutations. They concluded that the dosage of POGZ, specifically in neurons, is essential for normal learning in a habituation paradigm.
26739615 White et al 2016. They identified de novo heterozygous truncating variants in POGZ in 5 unrelated individuals. Careful review of the phenotypes revealed shared features that included developmental delay, ID, hypotonia, behavioral abnormalities and similar facial characteristics. Variable features included short stature, microcephaly, strabismus and hearing loss. They suggested that loss of function variants in POGZ lead to an identifiable syndrome of neurodevelopmental disorders with specific phenotypic traits.

Haploinsufficiency phenotype comments:

Heterozygous mutation in POGZ can cause White-Sutton syndrome (OMIM 616364). WHSUS is a neurodevelopmental disorder characterized by delayed psychomotor development shows in infancy, and a characteristic constellation of dysmorphic facial features. A big number of patients also have autism. In Allelic Variants 614787.0001, there is patient with White-Sutton syndrome, was identified with a heterozygous de novo 1 bp deletion in the POGZ gene, resulting in frameshift and premature termination (Leu1119CysfsTer). 614787.0002. In a girl with White-Sutton syndrome, they identified a heterozygous de novo A-to-T transversion at chromosome coordinate g.151,378,800 (chr1.151,378,800A-T, GRCh37) in the exon 19 of POGZ gene, resulting in a Leu904-to-ter substitution, predicted to result in a loss of function.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity