Uncombable hair and atopic dermatitis in a case of tricho‐dento‐osseous syndrome

Abstract

Abbildung 1: Struppige, zu Berge stehende, unkämmbare Haare sowie ausgeprägtes atopisches Ekzem bei einer Patientin mit TDO-Syndrom.

<i>DLX3 </i>Homeodomain Mutations Cause Tricho-Dento-Osseous Syndrome with Novel Phenotypes

“…Similar analyses by PolyPhen give significant positionspecific independent counts score differences for these amino acid changes (2.745 and 2.483, respectively), which arise from a strong positive score for the reference residue and negative scores for the observed alternative residue. We also tested the reported mutation I175T [Mayer et al, 2010] and obtained similar results, with the exception that in analysis of the homeodomain only, SIFT did not report threonine as not tolerated (score 0.09).…”

“…Common to these mutations is that they recode and truncate the C-terminal transactivating domain of the DLX3 protein and do not affect the homeodomain. The third mutation was a de novo missense mutation, c.524 1 C, replacing an isoleucine at position 175 with a threonine, and, like the mutations described in this paper, it affects a conserved residue in the homeodomain [Mayer et al, 2010]. This de novo mutation was associated with uncombable hair, atopic dermatitis, taurodontic teeth, enamel hypoplasia and dental infections in an 8-year-old child.…”

“…The same mutation was since identified in additional families, in which the disease was considered as representing a variant of TDO with an attenuated phenotype Wright et al, 2008]. The third mutation described so far, a missense mutation in the homeobox, was identified in a single patient with kinky hair, enamel defects and atopic dermatitis [Mayer et al, 2010].…”

“…Thus far, 3 causative mutations have been identified, all located in the DLX3 homeobox gene [Price et al, 1998a;Dong et al, 2005;Mayer et al, 2010]. The first identified mutation, a 4-bp deletion downstream of the homeobox observed in multiple families [Price et al, 1998b], results in typical signs of TDO as described above.…”

Neural Crest Deletion of Dlx3 Leads to Major Dentin Defects through Down-regulation of Dspp

“…Thus far, five mutations in DLX3 have been associated with TDO syndrome, all of which have an autosomal dominant mode of inheritance. The clinical observations associated with the different mutations in DLX3 reported so far are associated with highly penetrant tooth defects, and with more variable defects in hair and bone (1)(2)(3)(4)(5)(6). Furthermore, dental defects are the most debilitating trait of TDO patients who are highly susceptible to infections and abscesses.…”