A novel c.1037C > G (p.Ala346Gly) mutation in TP63 as cause of the ectrodactyly-ectodermal dysplasia and cleft lip/palate (EEC) syndrome.

Leandro Ucela Alves,Eliete Pardono,Paulo A Otto,Regina Célia Mingroni Netto

doi:10.1590/s1415-475738120140125

Leandro Ucela Alves, Eliete Pardono + Show 2 more

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https://doi.org/10.1590/s1415-475738120140125

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Abstract

Ectrodactyly – ectodermal dysplasia and cleft lip/palate (EEC) syndrome (OMIM 604292) is a rare disorder determined by mutations in the TP63 gene. Most cases of EEC syndrome are associated to mutations in the DNA binding domain (DBD) region of the p63 protein. Here we report on a three-generation Brazilian family with three individuals (mother, son and grandfather) affected by EEC syndrome, determined by a novel mutation c.1037C > G (p.Ala346Gly). The disorder in this family exhibits a broad spectrum of phenotypes: two individuals were personally examined, one presenting the complete constellation of EEC syndrome manifestations and the other presenting an intermediate phenotype; the third affected, a deceased individual not examined personally and referred to by his daughter, exhibited only the split-hand/foot malformation (SHFM). Our findings contribute to elucidate the complex phenotype-genotype correlations in EEC syndrome and other related TP63-mutation syndromes. The possibility of the mutation c.1037C > G being related both to acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome and SHFM is also raised by the findings here reported.

Highlights

Ectrodactyly-ectodermal dysplasia and cleft lip/palate (EEC) syndrome (OMIM 604292) is a rare autosomaldominant disorder characterized by dry or eczematous skin, sparse hair on the scalp, eyebrows and eyelashes, nail dystrophy and hypodontia, in addition to ectrodactyly and orofacial cleft
EEC is one out of five distinct ectodermal dysplasia (ED) syndromes caused by mutations in this gene, which include, besides EEC, acro-dermato-ungual-lacrimal-tooth syndrome (ADULT, OMIM 103285), ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC, OMIM 106260), limb-mammary syndrome (LMS, OMIM 603543), and Rapp-Hodgkin syndrome (RHS, OMIM 129400)
Nonsyndromic split hand/foot malformation (SHFM4, OMIM 605289) and, very rarely, nonsyndromic cleft lip may be caused by mutations in this same TP63 gene (Leoyklang et al, 2006; Rinne et al, 2006)

Summary

Introduction

Ectrodactyly-ectodermal dysplasia and cleft lip/palate (EEC) syndrome (OMIM 604292) is a rare autosomaldominant disorder characterized by dry or eczematous skin, sparse hair on the scalp, eyebrows and eyelashes, nail dystrophy and hypodontia, in addition to ectrodactyly and orofacial cleft. Most EEC cases, if not all, result from mutations in the TP63 gene, and more than 200 cases have already been reported in the literature (Clements et al, 2009).

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Conclusion