Abstract
ObjectivesEctrodactyly ectodermal dysplasia cleft lip/palate (EEC) syndrome and limb-mammary syndrome (LMS) share a similar phenotype and the same pathogenic gene, which complicates the ability to distinguish between these diagnoses. The current study aims to identify a potential and practical clinical biomarker to distinguish EEC from LMS.MethodsTwo EEC pedigrees and one LMS pedigree that have been previously reported were reanalyzed. After confirmation of the causative mutations for these new patients, whole-genome expression microarray analysis was performed to assess the molecular genetic changes in these families.ResultsFive new patients with classic symptoms were reported, and these individuals exhibited the same mutation as their relatives (c.812 G>C; c.611G>A; and c.680G>A). According to the whole genome expression results, the EEC patients exhibited different gene expression characteristics compared with the LMS patients. More than 5,000 genes were differentially expressed (changes >2 or <0.5-fold) among the EEC patients, LMS patients and healthy individuals. The top three altered pathways have been implicated in apoptosis, the hematopoietic cell lineage and the Toll-like receptor signaling pathway.ConclusionOur results provide additional clinical and molecular information regarding EEC and LMS and suggest that peripheral blood cytokines may represent a promising clinical biomarker for the diagnosis of these syndromes.
Highlights
According to the whole genome expression results, the ectodermal dysplasia cleft lip/palate (EEC) patients exhibited different gene expression characteristics compared with the limb-mammary syndrome (LMS) patients
Our results provide additional clinical and molecular information regarding EEC and LMS and suggest that peripheral blood cytokines may represent a promising clinical biomarker for the diagnosis of these syndromes
Ectodermal dysplasia cleft lip/palate (EEC) syndrome (#OMIM 604292), which is characterized by split hands and feet, ectodermal dysplasia, and cleft lip and/or cleft palate, is a rare inherited condition
Summary
Ectodermal dysplasia cleft lip/palate (EEC) syndrome (#OMIM 604292), which is characterized by split hands and feet, ectodermal dysplasia, and cleft lip and/or cleft palate, is a rare inherited condition. EEC shares clinical features with acro-dermato-ungual-lacrimaltooth (ADULT) syndrome (#OMIM 103285), ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome (#OMIM 106260), limb-mammary syndrome (LMS) (#OMIM 603543), orofacial cleft 8 (#OMIM 129400), and Rapp-Hodgkin ectodermal dysplasia (RHS) (#OMIM 129400). The phenotypic spectrum and variable expressivity make the clinical diagnosis and classification of these syndromes difficult [5]. These syndromes are caused by mutations in the same gene, i.e., the tumor protein p63 (TP63) gene [6]. The TP63 gene is a key regulator of ectodermal, orofacial and limb development. It is located at 3q28 and has 15 exons. Multiple transcript variants of the TP63 gene, which involve alternative splicing and different promoters, encode six isoforms, and the full-length TP63 protein contains 448 amino acids [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
