Examination of genotypic and phenotypic characteristics in patients with developmental disorders of ectoderm

Disorders that occur during the formation and differentiation of ectodermal structures are associated with various clinical pictures. More than 150 subtypes of ectodermal dysplasia have been described, which is characterized by abnormal developmental findings in two or more tissues of ectodermal origin. Hypohidrotic ectodermal dysplasia (HED), which affects teeth, hair follicles and sweat glands, is the most frequently reported disease in this group. Non-syndromic clinical forms affecting a single ectodermal structure are also frequently detected. Pathogenic changes in the genes encoding proteins that regulate signal transmission between the epithelial and mesenchymal layers during embryonic development are known to cause developmental disorders of ectoderm. In our study, we aimed to investigate DNA variants in a total of 25 cases, 12 of which were diagnosed with HED and 13 with isolated ectodermal anomaly, using the next generation sequencing method. In HED cases EDA, EDAR, EDARADD, EDA2R, NEMO, TRAF6 and WNT10A genes which are known to cause this disease were examined, while in other cases, exome sequencing method was preferred. Genotype-phenotype correlation analyses were performed by evaluating the characteristics of the detected variants and clinical findings of the cases. In 76% of the cases, clinically relevant DNA sequence variants were detected in genes associated with the development of ectodermal structures. Approximately 35% of the variants found were evaluated as novel. As the result of our study, important data were obtained regarding the genotypic characteristics underlying the phenotypic findings seen in developmental disorders of ectoderm. Keywords: Ectodermal dysplasia, next generation sequencing, variant analysis