Journal Article

Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63

Pascal H. G. Duijf, Kaate R. J. Vanmolkot, Peter Propping, Waltraut Friedl, Elmar Krieger, Frank McKeon, Volker Dötsch, Han G. Brunner and Hans van Bokhoven

in Human Molecular Genetics

Volume 11, issue 7, pages 799-804
Published in print April 2002 | ISSN: 0964-6906
Published online April 2002 | e-ISSN: 1460-2083 | DOI:
Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63

Show Summary Details


The transcriptional co-activator p63 is of crucial importance for correct development of the limbs, ectodermal appendages (skin, nails, teeth, hair, glands), lip and palate. Mutations in the p63 gene are found in a number of human syndromes, including ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome, limb-mammary syndrome (LMS), Hay–Wells syndrome and in non-syndromic split-hand/split-foot malformation (SHFM). Each syndrome has a specific pattern of mutations with different functional effects in in vitro functional assays. We report a mutation R298Q in acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome, another EEC-like condition. The mutation is located in the DNA binding domain of p63, which harbors almost all EEC associated mutations. However, unlike mutations in EEC syndrome, the R298Q ADULT syndrome mutation does not impair DNA binding. Rather, the mutation confers novel transcription activation capacity on the ΔN-p63γ isoform, which normally does not possess such activity. These results confirm that ADULT syndrome is a clinically as well as molecularly distinct member of the expanding p63 mutation family of human malformation syndromes. Our results further show that p63 contains a second transactivation domain which is normally repressed and can become activated by mutations in the DNA binding domain of p63.

Journal Article.  4805 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.