Kö nig B, Landthaler M, et al. Tattoo pigments are cleaved by laser light-the chemical analysis in vitro provide evidence for hazardous compounds. Photochem Photobiol 2004;80: 185e90. Wilmer JL, Kligerman AD, Erexson GL. Sister chromatid exchange induction and cell cycle inhibition by aniline and its metabolites in human fibroblasts. Environ Mutagen 1981;3: 627e38. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.

The physiology of human skin pigmentation is varied and complex, with an extensive melanogenic paracrine network involving mesenchymal and epithelial cells, contributing to the regulation of melanocyte survival and proliferation and melanogenesis. Mutations in several genes, involving predominantly the KIT ligand/c-Kit and Ras/mitogen-activated protein kinase signalling pathways, have been implicated in a spectrum of diseases in which there is hyperpigmentation, hypopigmentation or both. Here, we report on a 12-year-old girl from Taiwan with a 6-year history of diffuse progressive skin hyperpigmentation resulting from a different aetiology: an inborn metabolic disorder of vitamin B12 (cobalamin), designated cblJ. Using whole-exome sequencing we identified a homozygous mutation in ABCD4 (c.423C>G; p.Asn141Lys), which encodes an ATP-binding cassette transporter with a role in the intracellular processing of cobalamin. The patient had biochemical and haematological evidence of cobalamin deficiency but no other clinical abnormalities apart from a slight lightening of her previously black hair. Of note, she had no neurological symptoms or signs. Treatment with oral cobalamin (3 mg daily) led to metabolic correction and some reduction in the skin hyperpigmentation at the 3-month follow-up. This case demonstrates that defects or deficiencies of cobalamin should be remembered in the differential diagnosis of diffuse hyperpigmentary skin disorders.

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The term "cavernous hemangioma" has been used to describe vascular anomalies with histology featuring dilated vascular spaces, vessel walls consisting mainly of fibrous stromal bands lined by a layer of flattened endothelial cells, and an irregular outer rim of interrupted smooth muscle cells. Hepatic hemangiomas (HH) and cutaneous venous malformations (cVM) share this histologic pattern, and we examined lesions in both tissues to identify genetic drivers. Paired wholeexome sequencing of lesional tissue and normal liver from HH subjects revealed a recurrent GJA4 c.121G>T, p.Gly41Cys somatic mutation in 4 of 5 unrelated cases, and targeted sequencing in paired tissue from 9 additional HH subjects identified the same mutation in 8. In cutaneous lesions, paired targeted sequencing in 5 cVMs and normal epidermis, found the same GJA4 c.121G>T, p.Gly41Cys somatic mutation in 3. GJA4 encodes gap junction protein alpha 4, also called connexin 37 (Cx37), and the p.Gly41Cys mutation falls within the first transmembrane domain at a residue highly conserved among vertebrates. We investigated the impact of the Cx37 mutant via lentiviral transduction of primary human endothelial cells. We found that the mutant induced changes in cell morphology and led to non-canonical activation of SGK1, a serine/ threonine kinase known to regulate cell proliferation and apoptosis. Treatment with spironolactone, an inhibitor of angiogenesis, suppressed SGK1 activation and reversed changes in cell morphology. These findings identify a recurrent somatic GJA4 c.121G>T mutation as a driver of hepatic and cutaneous venous malformations, revealing a new pathway for vascular anomalies, with spironolactone a potential pathogenesis-based therapy. LB732Intravenous gentamicin therapy in adult junctional and recessive dystrophic Epidermolysis Bullosa with nonsense mutations does not result in sustained clinical improvement

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare type of epidermal nevus involving the eccrine acrosyringia. It typically presents as asymptomatic linear keratotic papules and plaques along the lines of Blaschko and predominantly affects the extremities. This disease has recently been linked to somatic mutations within the GJB2 locus. Only four GJB2 mutations have been previously documented for PEODDN, and the underlying genetic basis remains inconclusive. Herein, we report an 18‐year‐old female with a hyperkeratotic plaque on the dorsa of the proximal interphalangeal joint of her right ring finger, as well as multiple small hyperkeratotic papules linearly distributed on the lateral sides of her fingers occurring since birth. Histopathological results revealed prominent parakeratotic cornoid lamella‐like tiers at the opening of the eccrine secretory ducts. Whole‐exome sequencing of the affected skin tissue revealed a heterozygous germline mutation and a postzygotic somatic mutation in GJB2. In summary, this study presents a case of PEODDN with compound heterozygous mutations in GJB2, which broadens the genetic spectrum of this disease entity and implies a possible role for second‐hit mutations in the pathogenesis of PEODDN.