Introduction: Ectodermal dysplasias (ED) are a group of approximately 200 clinical and congenital syndromes characterized by alterations in the development and homeostasis of two or more ectodermal structures. There is one case per one million people and one case per 17000 newborns worldwide. The molecular causes of ED involve many genes and multiple developmental pathways. The genes causing ED act through pathogenetic mechanisms in the EDA/EDAR/EDARADD signalling pathway and regulatory pathways such as NEMO, WNT, TP63, EVC2, among others. The clinical presentation is characterized by hypohidrosis, hypodontia or anodontia, hypotrichosis, dermal alterations, craniofacial and limb malformations, and other clinical manifestations. Objective: The aim of our research was to identify the mutational spectrum in genes involved in the EDA, WNT and p63 signalling pathways associated with clinical alterations in the development of ectodermal structures in Mexican patients diagnosed with ectodermal dysplasia by whole exome sequencing (WES) analysis.Materials and methods: Genomic DNA were extracted from peripheral blood samples of ten mexican patients, with two or more clinical features related to structures of ectodermal origin. Subsequently, bioinformatic analysis of WES was performed, to determine exome sequencing quality, the FastQC software was used, then, the exomes were mapped against the reference genome GRCh38 with the BWA programme, filtered, realigned and the variants were identified and functionally classified in comparison against the database with the GATK and FUNCOTATOR software, finally, those variants were determined using databases such as ClinVar, OMIM, gnomAD, among others. Finally, the results were confirmed by Sanger sequencing.
Results: The bioinformatic analysis of WES supported the clinical diagnosis of Ellis Van Crevel syndrome, Curry-Hall syndrome, Ritscher-Schinzel 1 syndrome, hypohidrotic ectodermal dysplasia, EEC, SHFM4 and epidermolysis bullosa. Four patients required clinical re-evaluation to perform proper genotype-phenotype correlation.
Conclusions: We identified 6 pathogenic variants: three missense mutations in TP63, WASHC5 and EDA genes, two frame shift mutations in EVC2 gene, and one nonsense mutation in EVC2 gene, of which, five mutations are not reported in the databases, and one was previously reported as pathogenic.
Dr. Nancy Negrete-Torres1 is a Medical Doctor from the Universidad Nacional Autónoma de México, and MsC from the Instituto Politécnico Nacional (México). She Participated in various local Meetings. Her interest are clinical genetics, molecular biology, and bioinformatics. The present project is being developed for my master’s thesis and in collaboration with the Medical Surgeon Career of the Facultad de Estudios Superiores UNAM and the Escuela Nacional de Ciencias Biologicas IPN with the support of Dr. Glustein Pozo Molina and Dr. Isela Álvarez González, and the Centro Médico Nacional 20 de Noviembre, ISSSTE. She has participated in the Program for the Human Development Through Education and Scientific Research in Medicine.