Hemizygosity of delta-catenin (CTNND2) is associated with severe mental retardation in cri-du-chat syndrome

delta-catenin is an adherens junction protein involved in cell motility and expressed early in neuronal development. It was discovered as an interacto r with presenilin-1. The genomic structure of the human delta-catenin gene (Human Gene Nomenclature Committee-approved symbol CTNND2) was determined a nd mapped to 5p15.2, A deletion of this chromosomal region has been associa ted with the cri-du-chat syndrome (CDCS), a segmental aneusomy syndrome of 5p that is associated with an unusual high-pitched cry at birth, facial dys morphology, poor growth, and severe mental retardation. delta-catenin maps to a specific region in 5p15.2 that has been implicated in the mental retar dation phenotype, The breakpoints in patients with 5p terminal deletions we re characterized with respect to the severity of mental retardation and the physical location of the delta-catenin gene. A strong correlation was foun d between the hemizygous loss of delta-catenin and severe mental retardatio n. These findings and the properties of delta-catenin as a neuronal-specifi c protein, expressed early in development and involved in cell motility, su pport its role in the mental retardation of CDCS when present in only one c opy. (C) 2000 Academic Press.