Further evidence of the clinical and genetic heterogeneity of recessive transgressive PPK in the Mediterranean region

Abstract

Transgressive palmoplantar keratoderma (PPK) is the phenotypic hallmark of Mal de Meleda (MDM, MIM 24300). It is characterized by erythema and hyperkeratosis that extend to the dorsal face of the hands and feet. The disease is distributed worldwide and includes the Mediterranean population. The gene responsible for MDM, ARS (component B) mapped on chromosome 8qter, encodes for the SLURP-1 protein (Ly-6/uPAR related protein-1). A variety of mutations within the ARS gene have been shown to underlie MDM in different populations. Genetic heterogeneity of MDM is suspected. We have recently shown that three different homozygous mutations (82delT, C77R, C99Y) were responsible for MDM in 17 patients from Northern Tunisia belonging to eight unrelated consanguineous families. We report here a Tunisian family with three siblings presenting with recessive transgressive PPK closely resembling the MDM phenotype that excludes linkage to the ARS gene.

Mutations in the SLURP-1 gene underlie Mal de Meleda in three Pakistani families

“…All the mutations are homozygous except for one patient who is a compound heterozygote [20]. The mutations included missense, nonsense, deletion and splice site mutations [2]. Missense mutations in the gene are sufficient to lead to disease and most MDM mutations in SLURP-1 affect either expression, integrity, or stability of the protein [19].…”

“…The hyperkeratosis is associated with hyperhidrosis, macerations, pain, and malodor due to the superimposed bacterial and fungal infections. In addition, patients may develop perioral erythema, keratotic and lichenoid plaques over joints including elbows and knees, nail abnormalities, joint contractures and stiffness, brachydactyly, sclerodactyly and pseudoainhum [1][2][3]. Histological examination of the keratotic lesions reveals hyperorthokeratosis, acanthosis and focal areas of parakeratosis [4].…”

Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene

“…These findings further delineate the genetic heterogeneity of rare autosomal recessive diseases in Tunisia, as reported previously for different conditions. [22][23][24][25][26] Compared with the other two genes known to cause achromatopsia CNGA3 and CNGB3, GNAT2 is only a minor achromatopsia locus, which account for 2% of the cases. 7 As this is the largest sibship affected with GNAT2 achromatopsia, this family gave a unique opportunity for phenotype-genotype analysis and comparison to other complete achromatopsia subtypes.…”

Clinical and genetic investigation of pediatric cases of Wolff-Parkinson-White syndrome in Tunisian families

“…This finding was previously reported for cardiac diseases such as atrial septal defect, 23 and for several other disease types. [24][25][26] This finding provides evidence for the richness of the genetic background of the North African population.…”