DLX3 homeodomain mutations cause tricho-dento-osseous syndrome with novel phenotypes.
Tricho-dento-osseous syndrome (TDO) is a rare type of dominantly inherited ectodermal dysplasia so far described only in a few families and associated with 3 known mutations in the DLX3 homeobox gene. Here, we describe two families of Finnish origin that segregate features of TDO in several generations. The affected family members have sparse or curly/kinky hair at birth, markedly delayed or advanced dental maturity, defective tooth enamel and dentin, taurodontic molars, multiple dental abscesses and filling of tooth pulps with amorphous denticle-like material as well as an increased density and/or thickness of craniofacial bones. The disease is especially accentuated in one of the families in which the patients develop only lanugo-type hair and the dental abnormalities are severe. After mutational analysis of DLX3, we identified 2 missense mutations affecting the conserved homeodomain. We suggest that TDO is essentially caused by loss of function and haploinsufficiency of DLX3.
Institute of Dentistry, University of Helsinki, Helsinki, Finland. pekka.nieminen@helsinki.fi
Pekka
P
Nieminen
Pirjo-Liisa
PL
Lukinmaa
Heikki
H
Alapulli
Mirja
M
Methuen
Timo
T
Suojärvi
Sirpa
S
Kivirikko
Jaakko
J
Peltola
Mikko
M
Asikainen
Satu
S
Alaluusua
D000595:Amino Acid Sequence; D001483:Base Sequence; D019465:Craniofacial Abnormalities; D004252:DNA Mutational Analysis; D003744:Dental Enamel Hypoplasia / Q000235:genetics*; D005190:Family; D005387:Finland; D005801:Genes, Homeobox; D006201:Hair Diseases / Q000235:genetics*; D057895:Haploinsufficiency; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors