DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho-dento-osseous syndrome.
The distal-less homeobox gene DLX3 is expressed in a variety of tissues including placenta, skin, hair, teeth, and bone. Mutation of DLX3 (c.571_574delGGGG) causes the tricho-dento-osseous syndrome (TDO), characterized by abnormal hair, teeth, and bone. Evaluation of a kindred segregating the DLX3 c.561_562delCT mutation revealed distinct changes in the hair, teeth, and bones as has been observed with the DLX3 c.571_574delGGGG mutation. Previously, the DLX3 c.561_562delCT mutation was associated with autosomal dominant amelogenesis imperfecta with taurodontism. The present study shows that the DLX3 c.560_561delCT mutation causes an attenuated TDO phenotype with less severe hair, tooth, and bone manifestations compared with individuals having the DLX3 c.571_574delGGGG mutation. Careful phenotyping of individuals with allelic DLX3 mutations reveals marked differences in phenotypic severity indicating that the carboxy-terminus of the DLX3 protein is critical in determining its function during development in these different tissues.
Wright
J Timothy
JT
Department of Pediatric Dentistry, The University of North, Chapel Hill, North Carolina 27599, USA.Tim_Wright@Dentistry.unc.edu
Hong
Sung P
SP
Simmons
Darrin
D
Daly
Bill
B
Uebelhart
Daniel
D
Luder
Hans U
HU
D000567:Amelogenesis Imperfecta / Q000235:genetics*; D001483:Base Sequence; D001842:Bone and Bones / Q000002:abnormalities; D004476:Ectodermal Dysplasia / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D006197:Hair / Q000002:abnormalities; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors