2p15-16.1 microdeletion syndrome is a rare genetic disorder caused by a small deletion in one of the 46 chromosomes- chromosome 2. The precise genetic region responsible for the syndrome has been challenging to identify. Individuals with this syndrome present with intellectual disability, microcephaly, delayed growth, dysmorphic craniofacial features, and digital abnormalities.
However, recent reports indicate that four genes (XPO1, USP34, BCL11A, and REL) are commonly deleted in this syndrome.
A study in the current issue of JCI Insight describes eight new subjects with microdeletions in chromosomal region 2p15p16.1 and provides evidence that loss of XPO1, REL, and BCL11A underlie this syndrome.
Cells from patients had reduced expression of XPO1, USP34, BCL11A, and REL. Moreover, knock down of three of these homologous genes in zebrafish resulted in abnormalities consistent with patient phenotypes.
Together, the results of this study provide strong evidence that the combined loss of XPO1, BCL11A, and REL is responsible for 2p15p16.1 microdeletion syndrome.