TP63 gene mutation in ADULT syndrome

Amiel, Jeanne; Bougeard, Gaëlle; Francannet, Christine; Raclin, Valérie; Münnich, Arnold; Lyonnet, Stanislas; Frébourg, Thierry

doi:10.1038/sj.ejhg.5200676

Cited by 86 publications

(82 citation statements)

References 9 publications

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“…TP63, which was subsequently been proven to be the causative gene for ADULT syndrome, was present among these 12 selected genes. 11 A similar result was obtained for Noonan syndrome. Using 'skeletal and heart' as search terms, the number of genes from chromosome band 12q24.1 was 174.…”

Section: Resultssupporting

confidence: 74%

A new web-based data mining tool for the identification of candidate genes for human genetic disorders

et al. 2003

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Section: Resultssupporting

confidence: 74%

A new web-based data mining tool for the identification of candidate genes for human genetic disorders

et al. 2003

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“…3 Only two amino-acid residues are known to be mutated among ADULT syndrome patients: asparagine 6, which is in the putative second transactivation domain and arginine 298, which locates in the DNA binding domain. 4,5,7 Although R298 is in the DNA binding domain, it is functionally different from the EEC mutations, because its substitution by glutamine does not lead to a loss of DNA binding, but instead to a gain of transactivation activity of the deltaNp63gamma isoform. 6 Here, we report three further ADULT syndrome families with R298 mutations, either a R298Q or R298G.…”

Section: Introductionmentioning

confidence: 99%

Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene

et al. 2006

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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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“…2 Overlapping features with ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC or Hay -Wells syndrome, MIM 106260) and ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome (EEC, MIM 129900) have been previously reported. 3,4 Mutations of the TP63 gene have been identified in the following human malformation conditions: EEC syndrome, 5,6 AEC syndrome, 7 limb mammary syndrome (MIM 603543), 8 acrodermato-ungual-lacrimal-tooth syndrome (ADULT, MIM 103285), 9 nonsyndromic split-hand/foot malformation (MIM 183600), 10 isolated cleft lip/palate 11 and RHS. 12 Most of these entities are characterized by limb abnormalities that fit the split-hand/split-foot spectrum, ectodermal dysplasia affecting the hair, teeth, nails and sweat glands, and other malformations involving the face, the eyes and the urogenital system.…”

Section: Introductionmentioning

confidence: 99%

A new mutation in TP63 is associated with age-related pathology

et al. 2007

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Increases in the number of allelic malformation syndromes have led to their classification according to their pathogenesis rather than their clinical specific phenotype. TP63 (also known as TP73L) mutations have been identified in several such syndromes characterized by autosomal dominant transmission and various combinations of ectodermal dysplasia, limb malformations and orofacial clefting. TP63 has not yet been implicated in early aging phenotype in humans, even though p63 activates a program of cellular senescence and p63-compromised mice display features of accelerated aging. We report on a family with four affected adult females presenting with Rapp-Hodgkin syndrome (RHS), an autosomal dominant clinical entity that associates anhidrotic ectodermal dysplasia with cleft lip and palate. Features between RHS and EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) have led to the recent identification of mutations in the TP63 gene, located on 3q27, in this condition. Our patients present typical clinical features of RHS, but also ophthalmic anomalies such as corneal dystrophy and premature menopause (around 30 years). The latter findings have never been reported in this condition, and could be secondary to a new TP63 deletion that has been identified in this family.

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TP63 gene mutation in ADULT syndrome

Cited by 86 publications

References 9 publications

A new web-based data mining tool for the identification of candidate genes for human genetic disorders

A new web-based data mining tool for the identification of candidate genes for human genetic disorders

Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene

A new mutation in TP63 is associated with age-related pathology

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