ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
28139846 In 2017, Zarate et al. used whole exome sequencing (WES) on 11 individuals with SATB2-associated syndrome. The authors identified pathogenic variants in SATB2 in these individuals, all of which were confirmed de novo. Of these variants, 1 was a splice site, 5 were frameshifts, and 3 were nonsense variants.
28151491 In 2017, Bengani et al. described 20 individuals with SATB2 variants identified through whole exome sequencing. Analysis identified 19 different variants in SATB2, with the same variant existing in a pair of siblings. The majority of these individuals were identified from the DDD study. 11 of these variants were de novo loss of function variants, with 4 variants being nonsense variants, 5 being frameshift variants, and 2 being splice site variants. In addition to ID, many of the individuals in this study also had severe speech impairment, drooling, and craniofacial abnormalities including cleft palate and mild dental differences. Per the authors, ?The behavioral phenotype appeared to show the most marked discrepancy within the cohort, with both severe autistic features and friendly/happy personalities being recurrently reported.?

Haploinsufficiency phenotype comments:

Loss of function variants result in intellectual disability, cleft palate (reduced penetrance), and tooth abnormalities (variable expressivity). Of note: FitzPatrick et al. (2003) used high-resolution Fluorescence in situ hybridization studies to map two de novo translocation breakpoints in individuals with isolated cleft palate. In one individual the translocation break point disrupted the coding region of the SATB2 gene. In the second individual, the translocation break point mapped 130 kb 3' to SATB2 in a highly conserved region of noncoding DNA (PMID: 12915443)

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