Identification of novel homozygous <i><scp>SLURP</scp>1</i> mutation in a Javanese family with Mal de Meleda

Radiono, Sunardi; Pramono, Zacharias Aloysius Dwi; Oh, Glenda Guek Khim; Surana, Uttam; Widiyani, Syahfori; Danarti, Retno

doi:10.1111/ijd.13776

Cited by 8 publications

(8 citation statements)

References 33 publications

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“…Two additional J o u r n a l P r e -p r o o f examples are given by R96P and L98P mutations, which result in the incorrectly folded and inactive rSLURP-1 variants (Figures 2a,c and S1). F92 deletion as well as R96P and L98P mutations correspond to the severe MDM phenotype (Radiono et al 2017;Fischer et al 2001;Gurel et al 2019;Yerebakan et al 2003). Thus, mutations that impair the biosynthesis of correctly folded SLURP-1 and/or lead to complete inactivation of the protein correspond to the severe forms of MDM.…”

Section: Discussionmentioning

confidence: 99%

Biochemical Basis of Skin Disease Mal de Meleda: SLURP-1 Mutants Differently Affect Keratinocyte Proliferation and Apoptosis

Shulepko

Bychkov

Шенкарев

et al. 2021

Journal of Investigative Dermatology

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Section: Discussionmentioning

confidence: 99%

Biochemical Basis of Skin Disease Mal de Meleda: SLURP-1 Mutants Differently Affect Keratinocyte Proliferation and Apoptosis

Shulepko

Bychkov

Шенкарев

et al. 2021

Journal of Investigative Dermatology

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“…SLURP1, a member of the Ly6 superfamily, is downregulated during infection to help develop protective inflammation and inhibit leukocyte infiltration [41]. Mutation of the Slurp1 gene is related to mal de Meleda [42], which contributes to transgressive keratosis and keratoderma. SLURP1 was shown to have a suppressive effect on both the proliferation and migration of human corneal limbal epithelial cells [43].…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review on Cornea Epithelial-Stromal Homeostasis

Wong¹,

Poon²,

Bu³

et al. 2020

Ophthalmic Res

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Introduction: This review aims to summarise the role of different cells, genes, proteins and lipid in regulating cornea epithelial-stromal homeostasis. Methods: We performed an Entrez PubMed literature search using keywords “human,” “cornea,” “epithelial,” “stromal,” “homeostasis,” “fibrosis response,” and “pathogenesis” on 24th of September 2019, resulting in 35 papers, of which 18 were chosen after filtering for “English language” and “published within 10 years” as well as curation for relevance by the authors. Results: The 18 selected papers showed that corneal epithelial cells, fibroblasts and telocytes, together with genes such as Klf4, Pax6 and Id found in the cells, play important roles in achieving homeostasis to maintain corneal integrity and transparency. Proteins classified as pro-fibrotic ligands and anti-fibrotic ligands are responsible for regulating cornea stromal fibrosis and extracellular matrix deposition, thus regulators of scar formation during wound healing. Anti-inflammatory ligands and wound repairing ligands are critical in eliciting protective inflammation and promoting epithelial healing, respectively. Protein receptors located on cellular membrane play a role in maintaining intercellular connections as well as corneal hydration. Discussion/Conclusion: These studies prompt development of novel therapeutic strategies such as tear drops or ointments that target certain proteins to maintain corneal homeostasis. However, more in vitro and in vivo studies are required to prove the effectiveness of exogenous administration of molecules in improving healing outcome. Hence, future investigations of the molecular pathways highlighted in this review will reveal novel therapeutic tools such as gene or cell therapy to treat corneal diseases.

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“…To date, at least 20 different mutations in the SLURP1 gene associated with MDM have been reported in the published work. 4 The p.Gly86Arg loss-of-function mutation has been reported in patients from Taiwan, Korea, Palestine, Pakistan, Turkey and Libya. 2,5-7 SLURP1 belongs to the Ly-6/uPAR superfamily of receptors and secreted proteins, which participate in signal transduction, immune cell activation and cellular adhesion.…”

Section: Discussionmentioning

confidence: 99%

“…To date, at least 20 different mutations in the SLURP1 gene associated with MDM have been reported in the published work . The p.Gly86Arg loss‐of‐function mutation has been reported in patients from Taiwan, Korea, Palestine, Pakistan, Turkey and Libya …”

Section: Discussionmentioning

confidence: 99%

Abnormal keratinization and cutaneous inflammation in Mal de Meleda

Kudo

Ishiura

Tamura‐Nakano

et al. 2020

The Journal of Dermatology

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Mal de Meleda (MDM) is a rare, autosomal recessive form of palmoplantar keratoderma due to mutations in the gene, encoding for secreted lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein 1 (SLURP1). We report a four-year-old Taiwanese MDM female case whose biopsy specimen of hyperkeratotic lesions showed abnormal keratinization and cutaneous inflammation with characteristic transmission electron microscopic (TEM) findings and immunostaining results. The patient presented with pruritic and severely hyperkeratotic plaques on the bilateral palms and soles whichwere fringed with erythematous scaly areas. A homozygous c.256 G>A mutation, predicting a conversion of p.Gly86Arg, in SLURP1gene was detected. Histopathological examinations showed marked hyperkeratosis, acanthosis and hypergranulosis in the epidermis, accompanied by perivascular lymphocytic infiltrates in the dermis. The whole layers of the epidermis and perivascular infiltrates of the dermis were stained positive with anti-tumor necrosis factor alpha (TNFα) antibody in the biopsy specimen from the sole and the ankle. TEM examination of the biopsy specimen from the plantar hyperkeratotic plaque showed various-sized vacuoles surrounding nuclei of many keratinocytes in the spinous layer. In addition, there were numerous irregular keratohyaline granules in the granular layer. Several microorganisms and many lipid-like droplets were found in the thickened cornified layer. SLURP1 protein is known as a marker of late differentiation, predominantly expressed in the granular layer, and also known to have an inhibitory effect on TNFα release. Our results exhibited excessive TNFα expression in keratinocytes and perivascular infiltrates of the dermis, and several characteristic morphological observations of keratinocytes in MDM.

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

Abstract: 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.

Cited by 8 publications

References 33 publications

Biochemical Basis of Skin Disease Mal de Meleda: SLURP-1 Mutants Differently Affect Keratinocyte Proliferation and Apoptosis

Biochemical Basis of Skin Disease Mal de Meleda: SLURP-1 Mutants Differently Affect Keratinocyte Proliferation and Apoptosis

A Systematic Review on Cornea Epithelial-Stromal Homeostasis

Abnormal keratinization and cutaneous inflammation in Mal de Meleda

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