Homozygosity for the c.917A--<T (p.N306l) polymorphism in the EVER2/TMC8 gene of two sisters with epidermodysplasia verruciformis Lewandowsky-Lutz originally described by Wilhelm Lutz

BACKGROUND: Epidermodysplasia verruciformis Lewandowsky-Lutz (EV) is a rare genodermatosis, characterised by development of numerous verrucous skin lesions caused by specific genotypes of human papillomaviruses belonging to the beta-papillomavirus genus. The EV loci were mapped to chromosome 2p21-p24 (EV2) and 17q25 (EV1). On chromosome 17, 2 adjacent related genes--EVER1/TMC6 and EVER2/TMC8--were identified. We reinvestigated 2 patients originally described by Wilhelm Lutz in 1946 with the aim to document the natural course of the disease and confirm his diagnosis. METHODS: PCR fragments specific for exons with short flanking intron sequences of EVER1/TMC6 and EVER2/TMC8 genes from patients' DNA were amplified using sequence information. The single-nucleotide polymorphism (SNP) rs7208422 was studied, using restriction fragment length polymorphism analysis. RESULTS: In the index patient, we identified a homozygous TT genotype in exon 8 of the EVER2/TMC8 gene (c.917A--<T, p.N306I). The same mutation could thereafter be detected in her sister from paraffin-embedded skin. CONCLUSION: We have followed one of the first patients described with EV in Basel, Switzerland, in 1930 until today and demonstrated the TT genotype (SNP rs7208422) in the EVER2/TMC8 gene in this index patient and her sister. The results underline the possible relevance of SNP rs7208422 by influencing the susceptibility to beta-papillomaviruses and their oncogenic potential

Dronedarone, amiodarone and other antiarrhythmic drugs, and acute liver injuries: a case-referent study

International audienceBACKGROUND: Spontaneous reports of acute liver injuries (ALI) in patients taking dronedarone triggered an EMAalert in 2011. This study aimed to assess the risk of ALI for class III antiarrhythmic drugs controlling for the useof other potential ALI-inducing drugs.METHODS: Between 2010 and 2014, consecutive ALI cases (≥50 years-old) were identified across Germany. ALIwas defined as a new increase in at least one of the transaminases≥3 times the upper limit of normal (ULN)or≥2 ULN if alkaline phosphatase, with (“definite”case) or without (“biochemical”case) suggestive signs/symp-toms of ALI, excluding other liver diseases. Recruited community controls were matched to cases on gender, ageand inclusion date. Exposure to antiarrhythmic drugs and co-medication up to 2 years before ALI onset was in-formed by patients and confirmed by physicians' prescriptions. Adjusted Odds Ratios (aOR) were obtained fromconditional multivariable logistic regressions, adjusted for a multivariate disease risk score and co-medication.RESULTS: 252 cases and 1081 matched controls were included (59.1% females; mean age: 64 years). Exposure toclass III antiarrhythmic drugs was 4.0% in cases and 1.5% in controls, aOR = 3.6 (95% CI: 1.6–8.4). Associationswith exposure to dronedarone and amiodarone were respectively 3.1 (95% CI: 0.7–14. 8) and 5.90 (1.7–20.0).Restricting the analysis to definite or severe ALI cases did not change these results.CONCLUSIONS: Class III antiarrhythmic drugs were associated with ALI, amiodarone displaying the highest risk, andresults were robust to case definitions. Continued vigilance is needed for patients taking these drug