• SATB2-associated syndrome

This report describes SATB2-associated syndrome, an autosomal dominant disorder. The gene implicated in this disease is SATB2, which encodes a DNA-binding protein that specifically binds to genomic nuclear matrix attachment regions and participates in transcription regulation and chromatin remodeling. SATB2-associated syndrome shares phenotypes with Glass syndrome, which is caused by a small deletion on chromosome 2q32-q33; SATB2 is located within this region.

There is a single Drosophila gene orthologous to SATB2, dve, for which multiple genetic reagents have been generated, including classical loss-of-function mutations, RNAi-targeting constructs, and overexpression constructs. Dmel\dve is also orthologous to the human gene SATB1.

Animals homozygous for severe loss-of-function mutations of dve typically die during the larval stage. Overexpression of dve causes lethality or severe morphological phenotypes, depending upon expression of the driver.

UAS constructs of the human Hsap\SATB2 have been introduced into flies, including wild-type and variants implicated in this disease; see the 'Disease-Implicated Variants' table below. Overexpression of wild-type Hsap\SATB2 results in lethality or phenotypes similar to those observed for overexpression of Dmel\dve. Overexpression assays have been used to characterize variants associated with SATB2-associated syndrome, allowing categorization as loss-of-function or partial loss-of-function. Effects of three different variants affecting the same protein residue (Gly392) have been compared in the Drosophila system.

[updated Apr. 2025 by FlyBase; FBrf0222196]