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BioMed Research International
Volume 2013 (2013), Article ID 206803, 7 pages
http://dx.doi.org/10.1155/2013/206803
Research Article

Particular Mal de Meleda Phenotypes in Tunisia and Mutations Founder Effect in the Mediterranean Region

1Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire de Génomique Biomédicale et Oncogénétique (LR11IPT05), BP74, 13 Place Pasteur, Belvédère, 1002 Tunis, Tunisia
2Hôpital Farhat Hached, Département de Dermatologie, 4000 Sousse, Tunisia
3Hôpital La Rabta, Département de Dermatologie, 1007 Tunis, Tunisia
4Hôpital Habib Thameur, Département de Dermatologie, 1008 Tunis, Tunisia

Received 30 April 2013; Accepted 5 August 2013

Academic Editor: Helmut Schöfer

Copyright © 2013 Mbarka Bchetnia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.