Rinne T, Spadoni E, Kjaer KW et al.Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene. Eur J Hum Genet 14:904-910

1Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
European Journal of HumanGenetics (Impact Factor: 4.35). 09/2006; 14(8):904-10. DOI: 10.1038/sj.ejhg.5201640
Source: PubMed


The ADULT syndrome (Acro-Dermato-Ungual-Lacrimal-Tooth, OMIM 103285) is a rare ectodermal dysplasia associated with limb malformations and caused by heterozygous mutations in p63. ADULT syndrome has clinical overlap with other p63 mutation syndromes, such as EEC (OMIM 604292), LMS (OMIM 603543), AEC (106260), RHS (129400) and SHFM4 (605289). ADULT syndrome characteristics are ectrodactyly, ectodermal dysplasia, mammary gland hypoplasia and normal lip and palate. The latter findings allow differentiation from EEC syndrome. LMS differs by milder ectodermal involvement. Here, we report three new unrelated ADULT syndrome families, all with mutations of arginine 298. On basis of 16 patients in five families with R298 mutation, we delineate the ADULT syndrome phenotype. In addition, we have documented a gain-of-function effect on the dNp63gamma isoform caused by this mutation. We discuss the possible relevance of oral squamous cell carcinoma in one patient, who carries this p63 germline mutation.

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Available from: Cesare Danesino, Jul 15, 2014
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    • "Mutations in the DNA-binding domain of TP63 cause ectodermal dysplasia and facial clefting (EEC) and split hand/foot malformation (SHFM). Limb– mammary syndrome (LMS) and acro-dermato-ungual-lacrimaltooth (ADULT) syndrome are both rare disorders that appear to be caused by specific mutations in TP63 different from those seen in other disorders [Barrow et al., 2002; Brunner et al., 2002a,b; Rinne et al., 2006]. "
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    ABSTRACT: Ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome and Rapp-Hodgkin syndrome are well-characterized clinical entities caused by mutations in the TP63 gene. While AEC and Rapp-Hodgkin had been thought to be clinically distinct entities, the elucidation of their molecular etiology confirmed that they are a clinical continuum as opposed to distinct disorders. We have evaluated 17 patients with AEC syndrome using a systematic clinical approach. In our study, we have identified new features and others that were thought to occur only rarely. These include short stature and poor weight gain with preservation of head circumference in nearly all subjects, trismus in 35% and hypospadias in 78% of males. In addition, we describe the frequency of phenotypic features and demonstrate the extreme clinical variability in the largest cohort of AEC individuals reported in the literature thus far.
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    ABSTRACT: Mutations in the transcription factor gene p63 are causative for human developmental syndromes characterized by three main hallmarks: ectodermal dysplasia, limb malformations and orofacial clefting. Five different dominantly inherited human syndromes and two non-syndromic conditions have been linked to p63 gene defects. Ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome (EEC) is the most common p63-associated condition, since approximately 60 percent of all p63 mutations have been identified in EEC syndrome patients. Other p63-linked syndromes: AEC, LMS, ADULT and RHS, all show overlapping features of the three main disease characteristics. In contrast, isolated split hand/foot malformation (SHFM4) and non-syndromic cleft lip/palate (NSCL) only show one of the three main hallmarks. In this study I have tried to get more insight into the p63-associated diseases, their molecular disease mechanism and the role of p63 and its downstream signaling in these diseases.
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    ABSTRACT: Heterozygous mutations in the transcription factor gene p63 cause at least six different syndromes with various combinations of ectodermal dysplasia, orofacial clefting and limb malformations. Here we will present an update of mutations in the p63 gene together with a comprehensive overview of the associated clinical features in 227 patients. These data confirm the previously recognized genotype–phenotype associations. Moreover, we report that there is a large degree of clinical variability in each of the p63-associated disorders. This is illustrated by the different phenotypes that are seen for the five-hotspot mutations that explain almost 90% of all EEC syndrome patients. © 2006 Wiley-Liss, Inc.
    No preview · Article · Jul 2006 · American Journal of Medical Genetics Part A
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