No abstract

Mal de Meleda (MDM) is a rare, autosomal recessive form of palmoplantar keratoderma. It is characterized by erythema and hyperkeratosis of the palms and soles that progressively extend to the dorsal surface of the hands and feet. It is caused by mutations in SLURP-1 gene encoding for secreted mammalian Ly-6/uPAR-related protein 1 (SLURP-1). We performed mutational analysis by direct sequencing of SLURP-1 gene in order to identify the genetic defect in three unrelated families (families MDM-12, MDM-13, and MDM-14) variably affected with transgressive palmoplantar keratoderma. A spectrum of clinical presentations with variable features has been observed from the pronounced to the transparent hyperkeratosis. We identified the 82delT frame shift mutation in the SLURP-1 gene in both families MDM-12 and MDM-13 and the missense variation p.Cys99Tyr in family MDM-14. To date, the 82delT variation is the most frequent cause of MDM in the world which is in favour of a recurrent molecular defect. The p.Cys99Tyr variation is only described in Tunisian families making evidence of founder effect mutation of likely Tunisian origin. Our patients presented with very severe to relatively mild phenotypes, including multiple keratolytic pits observed for one patient in the hyperkeratotic area which was not previously reported. The phenotypic variability may reflect the influence of additional factors on disease characteristics. This report further expands the spectrum of clinical phenotypes associated with mutations in SLURP1 in the Mediterranean population.

Neonatal pemphigus vulgaris is a rare autoimmune disease that is caused by transplacental passage of pemphigus vulgaris autoantibodies. The association of maternal pemphigus vulgaris with neonatal disease pemphigus vulgaris has been only rarely reported. We describe an infant with pemphigus vulgaris born to a mother whose disease was in remission.

Beta-blocking medications are rarely associated with drug-induced lupus erythematosus syndrome and have never been incriminated as a cause of subacute lupus erythematosus (SCLE). We present herein the first case of SCLE induced by acebutolol. A 57-year-old woman presented with a 1-month history of a cutaneous eruption of the photoexposed areas. One month ago, the patient had started a treatment with oral acebutolol to cure a hypertension of 1-year evolution. Physical examination revealed erythematous scaly annular plaques, involving the face, arms and trunk. Immunologic serology findings revealed a positive titer of antinuclear antibodies up to 1/1,280 with positivity of antihistone and Ro/SSA antibodies. Acebutolol was stopped, and the lesions cleared completely 4 months later. Literature data, along with our case, suggest a link between acebutolol therapy and the onset of a lupus syndrome. Although this is the first report of acebutolol-induced SCLE, we should be aware of this occurrence, and avoidance of acebutolol is recommended in patients with stigmata of lupus erythematosus

Darier's disease (DD, MIM 124200) also known as Darier-White disease and keratosis follicularis, is a rare autosomal dominant skin disorder characterized by warty papules and plaques in the seborrheic area (central trunk, flexures, scalp, and forehead). Pathogenic mutations in the ATP2A2 gene encoding the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) 2 gene underlie the disease. In the present study, we performed genetic investigation of three unrelated Tunisian families affected by DD. Mutation screening was performed by direct sequencing of the coding region and exon/intron boundaries of the ATP2A2 gene. Patients in the 3 studied families exhibited classical DD phenotype. DD was associated with neurological and cardiac disorders in one family. Two novel mutations were identified: a missense mutation (R559Q) and a frameshift mutation (1713-1714 del 2A). Both pathogenic mutations are located in exon 13 of the ATP2A2 gene and affected the ATP-binding site of the SERCA2 protein. In one family, no mutation was found within the coding region and exon/intron boundaries of the ATP2A2 gene. Our findings provide further evidence for the genetic heterogeneity of DD in Tunisia and that most mutations involved in this disease are family specific.