Identification of novel homozygous SLURP1 mutation in a Javanese family with Mal de Meleda

Abstract

Background: Mal de Meleda (OMIM# 248300; keratosis palmoplantaris transgrediens) is an autosomal recessive form of palmoplantar keratoderma, clinically characterized by sharp demarcated erythema and hyperkeratosis of the palms and soles that progress with age and extend to the dorsal aspects of the hands and feet. The mal de Meleda is caused by mutations in the SLURP1 gene that encodes secreted lymphocyte antigen 6/urokinase-type plasminogen receptor-related protein 1 (SLURP1). To date no reported cases from Indonesia. The aims of the study were to describe the typical features of mal de Meleda cases in a Javanese family in Indonesia and identify the mutation in the ARS B gene which encodes SLURP1.

Patients and methods: In this study, three Javanese patients, siblings from nonconsanguineous nonaffected parents, presented with classical symptoms of mal de Meleda. Genetic analysis screening SLURP1 gene was conducted for the specimens from the patients and other family members.

Results: A novel homozygous three-nucleotide deletion in exon 3, i.e. c.271-273TCTdel, was identified in the patients. Subcloning and sequencing revealed both parents (I.2 and I.3) and one of the father's siblings (I.1) carry heterozygous c.271-273TCTdel, while the other father's sibling (I.2), the mother's sister (I.4), and a healthy control matched the ethnicity of the family, showing normal sequence of the entire SLURP1.

Conclusion: This is the first mal de Meleda case of Javanese ethnicity to be documented, and the unique mutation has not previously been reported. The finding supports the notion that despite the rarity, SLURP1 mutation causing mal de Meleda is ubiquitous.