Impact of next generation sequencing on diagnostics in a genetic skin disease clinic.

[dystrophic epidermolysis bullosa]

Individuals with inherited skin diseases often pose one of the most difficult diagnostic challenges in dermatology . The hunt for the underlying molecular pathology may involve candidate gene screening or linkage analysis , which is usually determined by the initial history , the physical findings and laboratory tests . Recent technical advances in DNA sequencing , however , are shifting the diagnostic paradigm . Notably , next -generation sequencing allows a more comprehensive approach to diagnosing inherited diseases , with potential savings of both time and money . In the setting of a paediatric dermatology genetics clinic in Kuwait , we therefore performed whole-exome sequencing on seven individuals without a priori detailed knowledge of the patients ' disorders : from these sequencing data , we diagnosed X-linked hypohidrotic ectodermal dysplasia (two cases ), acrodermatitis enteropathica , recessive erythropoietic protoporphyria (two siblings ) and localized recessive dystrophic epidermolysis bullosa (two siblings ). All these groups of disorders are clinically and genetically heterogeneous , but the sequencing data proved inherently useful in improving patient care and avoiding unnecessary investigations . Our observations highlight the value of whole-exome sequencing , in combination with robust bioinformatics analysis , in determining the precise molecular pathology and clinical diagnosis in patients with genetic skin disorders , notably at an early stage in the clinical evaluation of these often complex disorders and thereby support a new paradigm for future diagnostics .

Diseases
Validation

Diseases presenting "hypohidrotic ectodermal dysplasia" symptom

dystrophic epidermolysis bullosa

erythropoietic protoporphyria

oligodontia

omenn syndrome

This symptom has already been validated