Whole-exome sequencing in the clinical setting: Establishing a foothold for precision medicine in genodermatoses and other diseases

@#The concept of “precision medicine” has been a mainstay in discourses about the future of medicine, although it was not until the completion of the Human Genome Project that genetic associations to Mendelian diseases have risen dramatically. Since genetic variations in most (85%) monogenic or oligogenic diseases reside in exons, whole-exome sequencing (WES) serves as a pivotal tool in the identification of causative variants in genodermatoses and other diseases, leading to efficient and timely diagnosis. Here, we share our current diagnosis protocol for genodermatoses using WES as a first-tier solution. Two cases are presented to demonstrate the process of identifying germline variants and one case for a somatic variant. In the first case, a germline missense mutation in COL7A1 (exon73:c.G6127A) was identified for a patient that presented with clinical symptoms of dystrophic epidermolysis bullosa (DEB). Immunofluorescence study revealed decreased collagen VII expression in the dermal-epidermal junction. In case 2, we detected a germline missense mutation in KRT16 (exon1:c.374A>G) in a patient with palmoplantar keratoderma (PPK) and congenital pachyonychia. Sanger sequencing and segregation analysis confirmed the variant detected in WES. For case 3, a patient with linear nevus comedonicus was found to have a somatic missense mutation in NEK9 (exon4:c.500T>C), which was only detected in the lesional DNA sample. Thus, WES shows great potential as a diagnostic tool for monogenic or oligogenic genodermatoses. Since omics is a technology-driven tool, we expect that reaching precision medicine is ever closer.

Cutaneous protothecosis: A case report

Introduction@#Cutaneous protothecosis usually presents as pyoderma-like lesions or infiltrating papules and plaques on the extensor side of the extremities. It can be misdiagnosed as eczema, pyoderma, or a fungal infection. Although it has been isolated from a swimming pool, sewers and rivers in the Philippines, there has been no reported case of cutaneous protothecosis in the country.@*Case summary@#A 78-year-old Taiwanese male farmer visited the dermatology clinic due to a six-month history of a large, pruritic erythematous plaque studded with papulopustules on his left forearm. A potassium hydroxide (KOH) examination showed negative for hyphae or spores. And a skin biopsy showed morula-like bodies, which were highlighted by the Periodic acid-Schiff stain.@*Conclusion@#We report a case of cutaneous protothecosis from Taiwan so Filipino dermatologists will be aware of the clinical and histopathologic manifestations and management of cutaneous protothecosis.

The practical diagnostic approach for hereditary Epidermolysis Bullosa in the era of next generation sequencing

@#The new era of molecular diagnostics has provided new insights in both routine clinical work and research in hereditary epidermolysis bullosa (EB). Several different approaches and techniques have provided significant advantages in terms of diagnostic accuracy, predict- ing prognoses, clarifying the pathogenesis, and developing new therapies. In many developing countries, however, modern laboratory techniques remain inaccessible. Therefore, a practical diagnosticmatrix has been developed to predictthe diagnosis and subtype of EB. In thisreview,we highlight themolecular and practicaltechniquesin diagnosing hereditary EB.

Early Intervention with High-Dose Steroid Pulse Therapy Prolongs Disease-Free Interval of Severe Alopecia Areata: A Retrospective Study

BACKGROUND: Spontaneous recovery of severe alopecia areata is rare and the condition is difficult to treat. OBJECTIVE: The aim of this study is to investigate and compare the effects and safety of steroid pulse therapy between oral and intravenous administrations between 1999 and 2010 at the Department of Dermatology, National Cheng Kung University Hospital. METHODS: Data were retrospectively retrieved. A satisfactory response was defined as more than 75% hair regrowth in the balding area. RESULTS: A total of 85 patients with more than 50% hair loss were identified and treated, with an overall satisfactory response rate of 51.8%. The mean follow-up time was 37.6 months, with a relapse rate of 22.7%. Patients with alopecia areata (hereafter, AA) of recent onset within one year showed higher response rates (p<0.001) and lower relapse rates compared to patients with AA persisting for more than 1 year. Further, even in patients with alopecia totalis, alopecia universalis or ophiasis type, early treatment resulted in a satisfactory response rate of 47% among the treated patients. In general, oral therapy was as effective and well-tolerated as intravenous therapy. CONCLUSION: The response rate is determined by disease severity and time of intervention, not by the administration form of steroid pulse therapy. Oral steroid pulse therapy can be considered as the first-line treatment for patients with severe AA of recent onset within one year.