A Review of Next‐Generation Genetic Testing for the Dermatologist

Abstract

Dermatologists have been placed in a prime position to make new genetic discoveries. Tissue is easily obtained from the skin or mucosa for the study of germline and somatic mosaic disorders. This, along with the recent development of next-generation sequencing, makes dermatology an exciting field with essentially endless possibilities for discovering genes responsible for disease, better understanding complex molecular pathways, and eventually developing targeted therapies. To take advantage of this great opportunity, a basic understanding of the advances in genetic testing is vital. Herein we give an overview of next-generation sequencing, including some of the applications it may be used for. We also review various study designs for genetic discovery, each of their benefits and downfalls, and how they may be applied to the study of dermatologic disease.

Genetic Testing in Dermatology: A Survey Analyzing Obstacles to Appropriate Care

“…Virtually all dermatologists, irrespective of practice setting or years of practice, needed genetic testing at some point; one‐third of participating dermatologists needed genetic testing more than six times per year. As the practice of medicine moves toward personalized medicine, there will be a growing need for dermatologists to integrate molecular analyses into clinical practice .…”

“…Virtually all dermatologists, irrespective of practice setting or years of practice, needed genetic testing at some point; one-third of participating dermatologists needed genetic testing more than six times per year. As the practice of medicine moves toward personalized medicine, there will be a growing need for dermatologists to integrate molecular analyses into clinical practice (4,11). Consistent with the diagnostic challenge that genodermatoses present, respondents reported that genetic testing was most necessary to make an accurate diagnosis, followed by the need to provide prognostic information and appropriate medical management.…”

Predictive phenotyping of inherited ichthyosis by next‐generation DNA sequencing

“…Clinically, one of the major challenges in assessing patients with ichthyosis – particularly in neonates and infants in whom the often nonspecific nature of generalized scaling does not point to a single clinicopathological entity – is to be able to make an early and accurate diagnosis . In this report, we demonstrate the use of WES to identify genotype and predict phenotype in the clinical setting of a neonate with a seemingly sporadic, nonspecific, generalized form of inherited ichthyosis …”

“…4 In this report, we demonstrate the use of WES to identify genotype and predict phenotype in the clinical setting of a neonate with a seemingly sporadic, nonspecific, generalized form of inherited ichthyosis. 5 We report a 7-month-old boy, born to an unrelated African father and Afro-Caribbean mother at a gestation period of 40 weeks and 4 days following an uneventful pregnancy. He was their first child and there was no significant family history.…”

A multistep approach to the diagnosis of rare genodermatoses

“…For germline mutations, DNA is usually obtained from blood (1–5 ml EDTA blood) or buccal mucosa swabs. For mosaic skin disorders caused by postzygotic mutations, such as nevi, molecular analysis should be performed on affected skin tissue, with the patient's unaffected (healthy) tissue acting as built‐in control .…”