De novo, deleterious sequence variants that alter the transcriptional activity of the homeoprotein PBX1 are associated with intellectual disability and pleiotropic developmental defects.

ABSTRACT: We present eight patients with de novo, deleterious sequence variants in the PBX1 gene. PBX1 encodes a three amino acid loop extension (TALE) homeodomain transcription factor that forms multimeric complexes with TALE and HOX proteins to regulate target gene transcription during development. As previously reported, Pbx1 homozygous mutant mice (Pbx1-/-) develop malformations and hypoplasia or aplasia of multiple organs, including the craniofacial skeleton, ear, branchial arches, heart, lungs, diaphragm, gut, kidneys, and gonads. Clinical findings similar to those in Pbx mutant mice were observed in all patients with varying expressivity and severity, including external ear anomalies, abnormal branchial arch derivatives, heart malformations, diaphragmatic hernia, renal hypoplasia and ambiguou

SUBMITTER: Slavotinek A 

PROVIDER: S-EPMC6455034 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature