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Open Access 01-12-2019 | Research article

Novel nonsense variants in SLURP1 and DSG1 cause palmoplantar keratoderma in Pakistani families

Authors: Abida Akbar, Claire Prince, Chloe Payne, James Fasham, Wasim Ahmad, Emma L. Baple, Andrew H. Crosby, Gaurav V. Harlalka, Asma Gul

Published in: BMC Medical Genetics | Issue 1/2019

Abstract

Background

Inherited palmoplantar keratodermas (PPKs) are clinically and genetically heterogeneous and phenotypically diverse group of genodermatoses characterized by hyperkeratosis of the palms and soles. More than 20 genes have been reported to be associated with PPKs including desmoglein 1 (DSG1) a key molecular component for epidermal adhesion and differentiation. Mal de Meleda (MDM) is a rare inherited autosomal recessive genodermatosis characterized by transgrediens PPK, associated with mutations in the secreted LY6/PLAUR domain containing 1 (SLURP1) gene.

Methods

This study describes clinical as well as genetic whole exome sequencing (WES) and di-deoxy sequencing investigations in two Pakistani families with a total of 12 individuals affected by PPK.

Results

WES identified a novel homozygous nonsense variant in SLURP1, and a novel heterozygous nonsense variant in DSG1, as likely causes of the conditions in each family.

Conclusions

This study expands knowledge regarding the molecular basis of PPK, providing important information to aid clinical management in families with PPK from Pakistan.

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Patel S, Zirwas M, English JC. Acquired palmoplantar keratoderma. Am J Clin Dermatol. 2007;8(1):1–1.PubMedCrossRef

Has C, Technau-Hafsi K. Palmoplantar keratodermas, clinical and genetic aspects. J Dtsch Dermatol Ges. 2016;149(2):3–142.

Guerra L, Castori M, Didona B, Castiglia D, Zambruno G. Hereditary palmoplantar keratodermas. Part I. non-syndromic palmoplantar keratodermas: classification, clinical and genetic features. J Eur Acad Dermatol Venereol. 2018;32(5):704–19.PubMedCrossRef

Sakiyama T, Kubo A. Hereditary palmoplantar keratoderma “clinical and genetic differential diagnosis”. J Dermatol. 2016;43(3):264–74.PubMedCrossRef

Fatović-Ferencić S, Holubar K. The portrait and paper of a forgotten hero--Luca Stulli (1772-1828) and the mal de Meleda of yesteryear: a 175-year anniversary. J Invest Dermatol. 2001;116(1):198.PubMedCrossRef

Bergqvist C, Kadara H, Hamie L, Nemer G, Safi R, Karouni M, Marrouche N, Abbas O, Hasbani DJ, Kibbi AG, Nassar D. SLURP-1 is mutated in mal de Meleda, a potential molecular signature for melanoma and a putative squamous lineage tumor suppressor gene. Int J Dermatol. 2018;57(2):162–70.PubMedCrossRef

Itin PH, Fistarol SK. Palmoplantar keratodermas. Clin Dermatol. 2005;23(1):15–22.PubMedCrossRef

Perez C, Khachemoune A. Mal de Meleda: a focused review. Am J Clin Dermatol. 2016;17(1):63–70.PubMedCrossRef

Fischer J, Bouadjar B, Heilig R, Huber M, Lefèvre C, Jobard F, Macari F, Bakija-Konsuo A, Ait-Belkacem F, Weissenbach J, Lathrop M. Mutations in the gene encoding SLURP-1 in mal de Meleda. Hum Mol Genet. 2001;10(8):875–80.PubMedCrossRef

10.

Tjiu JW, Lin PJ, Wu WH, Cheng YP, Chiu HC, Thong HY, Chiang BL, Yang WS, Jee SH. SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda. Br J Dermatol. 2011;164(1):47–53.PubMedCrossRef

11.

Lyukmanova EN, Shulepko MA, Kudryavtsev D, Bychkov ML, Kulbatskii DS, Kasheverov IE, Astapova MV, Feofanov AV, Thomsen MS, Mikkelsen JD, Shenkarev ZO. Human secreted Ly-6/uPAR related protein-1 (SLURP-1) is a selective allosteric antagonist of α7 nicotinic acetylcholine receptor. PLoS One. 2016;11(2):0149733.CrossRef

12.

Rickman L, Šimrak D, Stevens HP, Hunt DM, King IA, Bryant SP, Eady RA, Leigh IM, Arnemann J, Magee AI, Kelsell DP. N-terminal deletion in a desmosomal cadherin causes the autosomal dominant skin disease striate palmoplantar keratoderma. Hum Mol Genet. 1999;8(6):971–6.PubMedCrossRef

13.

Milingou M, Wood P, Masouye I, McLean WH, Borradori L. Focal palmoplantar keratoderma caused by an autosomal dominant inherited mutation in the desmoglein 1 gene. Dermatol. 2006;212(2):117–22.CrossRef

14.

Keren H, Bergman R, Mizrachi M, Kashi Y, Sprecher E. Diffuse nonepidermolytic palmoplantar keratoderma caused by a recurrent nonsense mutation in DSG1. Arch Dermatol. 2005;141(5):625–8.PubMedCrossRef

15.

Samuelov L, Sarig O, Harmon RM, Rapaport D, Ishida-Yamamoto A, Isakov O, Koetsier JL, Gat A, Goldberg I, Bergman R, Spiegel R. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat Genet. 2013;45(10):1244.PubMedPubMedCentralCrossRef

16.

Favre B, Plantard L, Aeschbach L, Brakch N, Christen-Zaech S, de Viragh PA, Sergeant A, Huber M, Hohl D. SLURP1 is a late marker of epidermal differentiation and is absent in mal de Meleda. J Invest Dermatol. 2007;127(2):301–8.PubMedCrossRef

17.

Arredondo J, Chernyavsky AI, Webber RJ, Grando SA. Biological effects of SLURP-1 on human keratinocytes. J Invest Dermatol. 2005;125(6):1236–41.PubMedCrossRef

18.

Grando SA, Pittelkow MR, Schallreuter KU. Adrenergic and cholinergic control in the biology of epidermis: physiological and clinical significance. J Invest Dermatol. 2006;126(9):1948–65.PubMedCrossRef

19.

Muslumanoglu MH, Saracoglu N, Cilingir O, et al. A novel mutation in the ARS (component B) gene encoding SLURP-1 in a Turkish family with mal de Meleda. Br J Dermatol. 2006;155(2):467–9.PubMedCrossRef

20.

21.

Taylor JA, Bondavalli D, Monif M, Yap LM, Winship I. Mal de Meleda in Indonesia: mutations in the SLURP1 gene appear to be ubiquitous. Australas J Dermatol. 2014;57(1):11–3.CrossRef

22.

Zhang J, Cheng R, Ni C, Liang J, Yao Z. First mal de Meleda report in Chinese mainland: two families with a recurrent homozygous missense mutation in SLURP-1. J Eur Acad Dermatol Venereol. 2015;30(5):871–3.PubMedCrossRef

23.

Shah K, Nasir A, Shahzad S, Khan S, Ahmad W. A novel homozygous mutation disrupting the initiation codon in the SLURP1 gene underlies mal de Meleda in a consanguineous family. Clin Exp Dermatol. 2016;41(6):675–9.PubMedCrossRef

24.

Hammers CM, Stanley JR. Desmoglein-1, differentiation, and disease. J Clin Invest. 2013;123(4):1419–22.PubMedPubMedCentralCrossRef

25.

Getsios S, Simpson CL, Kojima SI, Harmon R, Sheu LJ, Dusek RL, Cornwell M, Green KJ. Desmoglein 1–dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis. J Cell Biol. 2009;185(7):1243–58.PubMedPubMedCentralCrossRef

26.

Lovgren ML, McAleer MA, Irvine AD, Wilson NJ, Tavadia S, Schwartz ME, Cole C, Sandilands A, Smith FJD, Zamiri M. Mutations in desmoglein1 cause diverse inherited palmoplantar keratoderma phenotypes:implications for genetic screening. Br J Dermatol. 2017;176(5):1345–50.PubMedCrossRef

27.

Vodo D, O’Toole EA, Malchin N, Lahav A, Adir N, Saring O, Green KJ, FJD, Sprecher E. Striate palmoplantar kerato-derma resulting from a missense mutation in DSG1. Br J Dermatol 2018;179(3):755–757.PubMedCrossRef

28.

Hovorka O. E. Ehlers Mal de Meleda. Arch Dermatol Res. 1897;40:251–6.CrossRef

29.

Mitsuhashi Y, Hashimato I. Keratosis palmoplantaris Nagashima. Dermatol. 1989;179:231.

30.

Kabashima K, Sakabe JI, Yamada Y, Tokura Y. “Nagashima-type” keratosis as a novel entity in the palmoplantar keratoderma category. Arch Dermatol 2008;144(3):375–379.

31.

Kubo A, Shiohama A, Sasaki T, Nakabayashi K, Kawasaki H, Atsugi T, Sato S, Shimizu A, Mikami S, Tanizaki H, Uchiyama M. Mutations in SERPINB7, encoding a member of the serine protease inhibitor superfamily, cause Nagashima-type palmoplantar keratosis. Am J Hum Genet. 2013;93(5):945–56.PubMedPubMedCentralCrossRef

32.

Dua-Awereh MB, Shimomura Y, Kraemer L, Wajid M, Christiano AM. Mutations in the desmoglein 1 gene in five Pakistani families with striate palmoplantar keratoderma. J Dermatol Sci. 2009;53(3):192–7.PubMedPubMedCentralCrossRef

Title: Novel nonsense variants in SLURP1 and DSG1 cause palmoplantar keratoderma in Pakistani families
Authors: Abida Akbar
Claire Prince
Chloe Payne
James Fasham
Wasim Ahmad
Emma L. Baple
Andrew H. Crosby
Gaurav V. Harlalka
Asma Gul
Publication date: 01-12-2019
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2019
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-019-0872-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Novel nonsense variants in SLURP1 and DSG1 cause palmoplantar keratoderma in Pakistani families

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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