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 interactor with presenilin-1. The genomic structure of the human delta-catenin gene (Human Gene Nomenclature Committee-approved symbol CTNND2) was determined and mapped to 5p15.2. A deletion of this chromosomal region has been associated 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 dysmorphology, poor growth, and severe mental retardation. delta-catenin maps to a specific region in 5p15.2 that has been implicated in the mental retardation phenotype. The breakpoints in patients with 5p terminal deletions were characterized with respect to the severity of mental retardation and the physical location of the delta-catenin gene. A strong correlation was found between the hemizygous loss of delta-catenin and severe mental retardation. These findings and the properties of delta-catenin as a neuronal-specific protein, expressed early in development and involved in cell motility, support its role in the mental retardation of CDCS when present in only one copy.
Medina
M
M
Department of Neurology, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Marinescu
R C
RC
Overhauser
J
J
Kosik
K S
KS
D051186:Armadillo Domain Proteins; D001483:Base Sequence; D051177:Catenins; D015815:Cell Adhesion Molecules; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003001:Cloning, Molecular; D003410:Cri-du-Chat Syndrome / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007438:Introns; D010641:Phenotype; D010750:Phosphoproteins; D020161:Physical Chromosome Mapping; D000095002:Delta Catenin
D051186:Armadillo Domain Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D010750:Phosphoproteins; D000095002:Delta Catenin; C000722348:CTNND2 protein, human