Background Mutations in the SLC29A3 gene, which encodes the nucleoside transporter hENT3, have been implicated in syndromic forms of histiocytosis including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, Faisalabad histiocytosis and Familial Rosai–Dorfman disease (RDD). Herein, we report five new patients from a single family who present with phenotypes that associate features of H syndrome and Familial Rosai–Dorfman disease. Methods We investigated the clinical, biochemical, histopathological and molecular findings in five Tunisian family members' diagnosed with Familial RDD and/or H syndrome. The solute carrier family 29 (nucleoside transporters), member 3 (SLC29A3) gene was screened for molecular diagnosis using direct Sanger sequencing. Results Genetic analysis of all affected individuals revealed a previously reported missense mutation c.1088 G > A [p.Arg363Gln] in exon 6 of the SLC29A3 gene. Four affected members presented with clinical features consistent with the classical H syndrome phenotype. While their cousin’s features were in keeping with Familial Rosai–Dorfman disease diagnosis with a previously undescribed cutaneous RDD presenting as erythematous nodular plaques on the face. This report underlines the clinical variability of SLC29A3 disorders even with an identical mutation in the same family. Conclusion We report a rare event of 5 Tunisian family members' found to be homozygous for SLC29A3 gene mutations but showing a different phenotype severity. Our study reveals that despite a single mutation, the clinical expression of the SLC29A3 disorders may be significantly heterogeneous suggesting a poor genotype–phenotype correlation for the disease.

Background Porokeratosis (PK) is a group of rare acquired or inherited clonal keratinization disorders characterized by annular or linear hyperkeratotic plaques with central atrophy and raised borders. Cornoid lamella is the common histological feature between PK forms. Genes of the mevalonate pathway are implicated in the pathogenesis of this pathology. To date, the exact underlying molecular mechanisms remain misunderstood. Results In this study, we investigated two unrelated Tunisian families with heterogeneous PK for whom we reported a clinical heterogeneity with a simultaneous presence of three clinical forms of PK in two individuals. We identified two PMVK variants, nonsense and synonymous, in affected individuals and unaffected relatives. We suggest that the PK profiles of our Tunisian patients result from the germline nonsense mutation c.412A > T (p.R138*) responsible for the haploinsufficiency of the PMVK protein via the degradation of the mutant mRNA by the nonsense-mediated mRNA decay (NMD) mechanism and d a second hit postzygotic mutation in skin lesions. We suggest that the synonymous variant c.147A > G (p.E49=) could be a genetic predisposition factor increasing the susceptibility to the second hit mutation in the PMVK gene or another gene. Conclusion We report the first molecular characterization of PK within the Tunisian and North African populations. Our findings support the common molecular background of different clinical subtypes of PK and the fact that they can be considered a single disorder.

H Syndrome is a rare genodermatosis. It may include facial involvement such as : facial telangiectasia, both hypo- and hyperpigmented lesions, hirsutism, swollen cheeks due to subcutaneous infiltration and eczematous lesions. We describe a new facial phenotype with dermoscopic and histological features in the spectrum of non-Langerhans cell histiocytosis.