Search tips
Search criteria 


Logo of jmedgeneJournal of Medical GeneticsVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
J Med Genet. 1998 October; 35(10): 825–828.
PMCID: PMC1051457

A common DLX3 gene mutation is responsible for tricho-dento-osseous syndrome in Virginia and North Carolina families.


Tricho-dento-osseous syndrome (TDO) is characterised by a variable clinical phenotype primarily affecting the hair, teeth, and bone. Different clinical features are observed between and within TDO families. It is not known whether the variable clinical features are the result of genetic heterogeneity or clinical variability. A gene for TDO was localised recently to chromosome 17q21 in four North Carolina families, and a 4 bp deletion in the human distal-less 3 gene (DLX3) was identified in all affected members. A previous genetic linkage study in a large Virginia kindred with TDO indicated possible linkage to the ABO, Gc, and Kell blood group loci. To examine whether TDO exhibits genetic heterogeneity, we have performed molecular genetic analysis to determine whether affected members of this Virginia kindred have the DLX3 gene deletion identified in North Carolina families. Results show that affected subjects (n=3) from the Virginia family have the same four nucleotide deletion previously identified in the North Carolina families. A common haplotype for three genetic markers surrounding the DLX3 gene was identified in all affected subjects in the North Carolina and Virginia families. These findings suggest that all people with TDO who have been evaluated have inherited the same DLX3 gene deletion mutation from a common ancestor. The variable clinical phenotype observed in these North Carolina and Virginia families, which share a common gene mutation, suggests that clinical variability is not the result of genetic heterogeneity at the major locus, but may reflect genetic heterogeneity at other epigenetic loci or contributing environmental factors or both.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (843K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Lichtenstein JR, Warson RW. Syndrome of dental anomalies, curly hair and sclerotic bones. Birth Defects Orig Artic Ser. 1971 Jun;7(7):308–311. [PubMed]
  • Quattromani F, Shapiro SD, Young RS, Jorgenson RJ, Parker JW, Blumhardt R, Reece RR. Clinical heterogeneity in the tricho-dento-osseous syndrome. Hum Genet. 1983;64(2):116–121. [PubMed]
  • Kula K, Hall K, Hart T, Wright JT. Craniofacial morphology of the tricho-dento-osseous syndrome. Clin Genet. 1996 Dec;50(6):446–454. [PubMed]
  • Shapiro SD, Quattromani FL, Jorgenson RJ, Young RS. Tricho-dento-osseous syndrome: heterogeneity or clinical variability. Am J Med Genet. 1983 Oct;16(2):225–236. [PubMed]
  • Hart TC, Bowden DW, Bolyard J, Kula K, Hall K, Wright JT. Genetic linkage of the tricho-dento-osseous syndrome to chromosome 17q21. Hum Mol Genet. 1997 Dec;6(13):2279–2284. [PubMed]
  • Price JA, Bowden DW, Wright JT, Pettenati MJ, Hart TC. Identification of a mutation in DLX3 associated with tricho-dento-osseous (TDO) syndrome. Hum Mol Genet. 1998 Mar;7(3):563–569. [PubMed]
  • Rivas ML, Lichtenstein J, Bias WB. Possible linkage between the loci for the trichodentoosseous (TDO) syndrome and the ABO blood group system: genetic and clinical implications. Birth Defects Orig Artic Ser. 1974;10(10):255–260. [PubMed]
  • Wright JT, Kula K, Hall K, Simmons JH, Hart TC. Analysis of the tricho-dento-osseous syndrome genotype and phenotype. Am J Med Genet. 1997 Oct 17;72(2):197–204. [PubMed]
  • Lichtenstein J, Warson R, Jorgenson R, Dorst JP, McKusick VA. The tricho-dento-osseous (TDO) syndrome. Am J Hum Genet. 1972 Sep;24(5):569–582. [PubMed]
  • Melnick M, Shields ED, El-Kafrawy AH. Tricho-dento-osseous syndrome: a scanning electron microscopic analysis. Clin Genet. 1977 Jul;12(1):17–27. [PubMed]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Group