A novel mutation in the ARS (component B) gene encoding SLURP-1 in a Turkish family with mal de Meleda

Müslümanoğlu, Muhammed Hamza; Saracoglu, N.; Çilingir, Oğuz; Basmaci, T.; Ürer, Selim Murat; Sabuncu, İlham; Demir, Selma; Bademci, Güney; Artan, Sevilhan

doi:10.1111/j.1365-2133.2006.07288.x

Cited by 12 publications

(11 citation statements)

References 7 publications

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“…SLUrP-1 protein is involved in keratinocyte differentiation (15) and alterations of the protein can disturb normal skin development as has been found in patients with MDM (8,10,14,(16)(17)(18)(19)(20)(21)(22). The SLUrP-1 protein is encoded by the 3 exons of the SLURP1 gene (previously ARS) and contains a signal peptide as well as conserved cysteines important in forming disulphide bonds that are critical for the function of the protein.…”

Section: Discussionmentioning

confidence: 99%

Palmoplantar Keratoderma of the Gamborg-Nielsen Type is Caused by Mutations in the SLURP1 Gene and Represents a Variant of Mal de Meleda

Zhao¹,

Vahlquist²,

Virtanen³

et al. 2014

Acta Derm Venerol

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Palmoplantar keratoderma of the Gamborg-Nielsen type (PPK-GN) is a rare autosomal recessive skin disorder described in patients from Sweden. Mal de Meleda (MDM) is also a rare autosomal recessive inherited PPK first reported in 5 families from the island of Meleda. The 2 conditions phenotypically overlap and are characterised by palmoplantar erythematous hyperkeratotic plaques. The genetic background giving rise to PPK-GN has hitherto been unknown, whereas MDM is known to be caused by mutations in the gene encoding secreted Ly-6/uPAR-related protein 1, SLURP-1. In the present study we scrutinised individuals affected by PPK-GN for mutations in the SLURP1 gene and identified 2 different mutations. Fourteen Swedish patients were homozygous for a previously described mutation, c.43T>C, while one individual was a compound heterozygote with one copy of a novel mutation, c.280T>A, in addition to one copy of the c.43T>C mutation. Hereby we confirm that PPK-GN is an allelic variant of MDM.

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Section: Discussionmentioning

confidence: 99%

Palmoplantar Keratoderma of the Gamborg-Nielsen Type is Caused by Mutations in the SLURP1 Gene and Represents a Variant of Mal de Meleda

Zhao¹,

Vahlquist²,

Virtanen³

et al. 2014

Acta Derm Venerol

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“…Zhao et al suggest it may, if only for historical reasons [37]. Figure 2 [7,11,17,[32][33][34][35][36][38][39][40][41] shows an exon/intron map of the SLURP-1 gene and lists the mutation types and their location in Mal de Meleda (as well as the Gamborg-Nielsen variant).…”

Section: Genetics and Pathophysiologymentioning

confidence: 99%

“…c.1A>C (p. Met1Leu) [34] Ivs1+1G>A (alt splice site) [17] c.82delT (p.Cys28fs32X) [33] Ivs2+1G>A (alt splice site) [33] c.229T>C (p.Cys77Arg) [35] c.43T>C (p.Trp15Arg) [36] c.58+5G>T (alt splice site) [11] c.129C>A (p.C43X) [38] c.244C>T (p.Pro82Ser) [32] c.212G>A (p.Arg71His) [41] c.256G>C (p.Gly86Arg) [34] c.212G>C (p.Arg71Pro) [36] c.256G>A (p.Gly86Arg) [34] c.280T>A (p.Cys94Ser) [7] c.286C>T (p.Arg96Term) [33] c.293T>C (p.Leu98Pro) [39] c.296G>A (p.Cys99Tyr) [40] AD autosomal dominant, AR autosomal recessive, PPK palmoplantar keratoderma Reed et al [73] discussed effective treatment with oral 13-cis retinoid acid following failed treatment with corticosteroid, lactic acid, retinoid acid, and emollients. More recently, Gruber et al [32] showed effective treatment with oral acitretin 20 mg/day plus topical antimicrobial and keratolytic therapy.…”

Section: Intron 1 (405 Bp) Intron 2 (526 Bp)mentioning

confidence: 99%

Mal de Meleda: A Focused Review

Pérez

Khachemoune

2015

Am J Clin Dermatol

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Mal de Meleda is a rare autosomal recessive palmoplantar keratoderma (PPK) disease with an estimated prevalence of 1:100,000. Clinically, the onset of the disease is typically soon after birth and features a transgrediens (plantar surface progressing to dorsal surface) and progrediens (worsening with age) pattern of hyperkeratosis of the palms and soles. The disease can feature other potentially disfiguring effects on the hands and feet that can severely impact function. Histologically, the lesions show hyperkeratosis and acanthosis without epidermolysis in the epidermis, accompanied by perivascular lymphocytic infiltrate in the dermis. Secreted LY6/urokinase-type plasminogen activator receptor (uPAR)-related protein-1 (SLURP-1) genetic mutations are implicated in Mal de Meleda. SLURP-1 is involved in mediation of inflammation as well as keratinocyte apoptosis regulation. Because the disease is so rare, there are no set guidelines for management, but the accepted approach tends to include oral acitretin plus topical keratolytic therapy. Genetic counseling should also be offered. This focused review highlights the clinical and histological features, differential diagnoses, genetic background, and the current thoughts on management of Mal de Meleda.

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“…Met1Lys (Emirates Bedouin [15]); Ivs1 + 1G > A (Pakistani [16]); Trp15Arg (German [15], Scottish [3], and Dutch [17]); 82delT (Tunisian [3], Scottish [3], Algerian [3], Croatian [9], Kurdish [10], and Italian [11]); Ivs2 + 1G > A (Algerian [3]); Cys43Stop (Turkish [18]); Arg71Pro (Dutch [17]); Cys77Ala (Tunisian [4]); Pro82Ser (Turkish [19]); Gly86Arg (Palestinian [15], Turkish [15]), and Pakistani [16]), Korean [20], Taiwanese [21]); Arg96Stop (Croatian [9], Turkish [10], Korean [20], and Pakistani [16]); Lys98Pro (Turkish [22]); Cys99Tyr (Tunisian [12]); and Arg71His (patient was reported in a study from France, and the origin is not reported [23]).…”

Section: Figurementioning

confidence: 99%

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

Bchetnia

Laroussi

Youssef

et al. 2013

BioMed Research International

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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.

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A novel mutation in the ARS (component B) gene encoding SLURP-1 in a Turkish family with mal de Meleda

Cited by 12 publications

References 7 publications

Palmoplantar Keratoderma of the Gamborg-Nielsen Type is Caused by Mutations in the SLURP1 Gene and Represents a Variant of Mal de Meleda

Palmoplantar Keratoderma of the Gamborg-Nielsen Type is Caused by Mutations in the SLURP1 Gene and Represents a Variant of Mal de Meleda

Mal de Meleda: A Focused Review

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

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