Ectrodactyly-ectodermal dysplasia-clefting syndrome with unusual cutaneous vitiligoid and psoriasiform lesions due to a novel single point TP63 gene mutation

The p63 protein is a member of a highly-conserved family of transcription factors (p53/p73) which play a pivotal role in ectodermal and epidermal homeostasis as well as orofacial and limb development [1–4]. Novel data suggest its role in the control of senescence, fertility, hearing, neurodevelopment and even cardiogenesis [5–10]. The gene coding for p63 is located on chromosome 3q28 and consists of 14 exons [11]. It exerts its biologic functions through at least ten different protein isoforms, which are synthesized as a consequence of transcription from alternate promoters (TA and N) and alternative splicing (-, -,-, - and -) [12]. The p63 protein is expressed in the nuclei of keratinocytes (predominantly basal ones) of stratified epithelia (skin, tonsils, esophagus and ectocervix), transitional epithelia (urinary tract), simple epithelia (bronchial tree, acini of the breast and prostate, sebaceous and sweat glands), female and male germlines and also to some extent in the germinal centers of lymph nodes [13, 14]. Investigations on p63-deficient animals and humans bearing mutations in p63 shed light on cutaneous morphogenesis and pathophysiology and revealed p63 as a sentinel of epidermal commitment and differentiation, cell-cell adhesion and basement membrane formation [1, 2].
Heterozygous mutations in TP63 cause seven human developmental syndromes, which include: ADULT syndrome (OMIM 103285); ectrodactyly, ectodermal dysplasia with cleft lip/palate syndrome 3 (OMIM 604292); Hay-Wells syndrome (OMIM 106260); limb-mammary syndrome (OMIM 603543); orofacial cleft 8 (OMIM 129400); Rapp-Hodgkin syndrome (OMIM 129400); and split-hand/foot malformation 4 (OMIM 605289), all of which share at least one common feature [15]. However, the influence of specific mutations or positioning of mutated residues in specific domains on TP63-related pathology remains elusive.
Ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome 3 (EEC3) belongs to group 1 of ectodermal dysplasias according to a novel clinico-molecular classification [16, 17], which not only denotes involvement of two or more ectodermal derivatives but also encompasses its genetic background and pathogenic mechanism (regulatory changes in transcription and/or expression of genes – in this instance p63). We report here a new patient with EEC3 due to a new heterozygous p63 mutation, and discuss the genotypic-phenotypic correlations of this syndrome.
A 23-year-old man was...


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