Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene.
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.
Rinne
Tuula
T
1Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Spadoni
Emanuela
E
Kjaer
Klaus W
KW
Danesino
Cesare
C
Larizza
Daniela
D
Kock
Marianne
M
Huoponen
Kirsi
K
Savontaus
Marja-Liisa
ML
Aaltonen
Markku
M
Duijf
Pascal
P
Brunner
Han G
HG
Penttinen
Maila
M
van Bokhoven
Hans
H
D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D001120:Arginine; D002648:Child; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D013577:Syndrome; D014071:Tooth Abnormalities / Q000235:genetics; D015533:Transcriptional Activation
D001120:Arginine