Skip to main content

Advertisement

SpringerLink
Log in

Splicing mutation in MVK is a cause of porokeratosis of Mibelli

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Porokeratosis is a chronic skin disorder characterized by the presence of patches with elevated, thick, keratotic borders, with histological cornoid lamella. Classic porokeratosis of Mibelli (PM) frequently appears in childhood with a risk of malignant transformation. Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis with genetic heterogeneities, and mevalonate kinase gene (MVK) mutations have been identified in minor portion of DSAP families of Chinese origin. To confirm the previous findings about MVK mutations in DSAP patients and test MVK’s role(s) in PM development, we performed genomic sequence analysis for 3 DSAP families and 1 PM family of Chinese origin. We identified a splicing mutation of MVK gene, designated as c.1039+1G>A, in the PM family. No MVK mutations were found in three DSAP families. Sequence analysis for complementary DNA templates from PM lesions of all patients revealed a mutation at splice donor site of intron 10, designated as c.1039+1G>A, leading to the splicing defect and termination codon 52 amino acids after exon 10. Although no MVK mutations in DSAP patients were found as reported previously, we identified MVK simultaneously responsible for PM development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

PM:

Porokeratosis of Mibelli

DSAP:

Disseminated superficial actinic porokeratosis

MVK :

Mevalonate kinase gene

cDNA:

Complementary DNA

PCR:

Polymerase chain reaction

GADPH:

Glyceraldehyde-3-phosphate dehydrogenase

References

  1. Ammouri W, Cuisset L, Rouaghe S, Rolland MO, Delpech M, Grateau G, Ravet N (2007) Diagnostic value of serum immunoglobulinaemia D level in patients with a clinical suspicion of hyper IgD syndrome. Rheumatology (Oxford) 46:1597–1600

    Article  CAS  Google Scholar 

  2. Bozdag KE, Bicakci H, Ermete M (2004) Giant porokeratosis. Int J Dermatol 43:518–520

    Article  PubMed  Google Scholar 

  3. Cao HM, Wang ZY, Zhang GW, Liu CF, Pan CM, Zhao SX, Song ZY, Song HD, Zhang L (2012) Identification of a locus (DSP2) for disseminated superficial porokeratosis at chromosome 12q21.2-24.21. Clin Exp Dermatol 37:672–676

    Article  PubMed  CAS  Google Scholar 

  4. Cuisset L, Drenth JP, Simon A, Vincent MF, van der Velde Visser S, van der Meer JW, Grateau G, Delpech M, International Hyper-IgD Study Group (2001) Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome. Eur J Hum Genet 9:260–266

    Article  PubMed  CAS  Google Scholar 

  5. Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M (1999) Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group. Nat Genet 22:178–181

    Article  PubMed  CAS  Google Scholar 

  6. Frenkel J, Houten SM, Waterham HR, Wanders RJ, Rijkers GT, Duran M, Kuijpers TW, van Luijk W, Poll-The BT, Kuis W (2001) Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D. Rheumatology (Oxford) 40:579–584

    Article  CAS  Google Scholar 

  7. Hager EJ, Piganelli JD, Tse HM, Gibson KM (2012) Aberrant expression of costimulatory molecules in splenocytes of the mevalonate kinase-deficient mouse model of human hyper-IgD syndrome (HIDS). J Inherit Metab Dis 35:159–168

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Houten SM, Frenkel J, Rijkers GT, Wanders RJ, Kuis W, Waterham HR (2002) Temperature dependence of mutant mevalonate kinase activity as a pathogenic factor in hyper-IgD and periodic fever syndrome. Hum Mol Genet 11:3115–3124

    Article  PubMed  CAS  Google Scholar 

  9. Hospach T, Lohse P, Heilbronner H, Dannecker GE, Lohse P (2005) Pseudodominant inheritance of the hyperimmunoglobulinemia D with periodic fever syndrome in a mother and her two monozygotic twins. Arthritis Rheum 52:3606–3610

    Article  PubMed  CAS  Google Scholar 

  10. Houten SM, Koster J, Romeijn GJ, Frenkel J, Di Rocco M, Caruso U, Landrieu P, Kelley RI, Kuis W, Poll-The BT et al (2001) Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome. Eur J Hum Genet 9:253–259

    Article  PubMed  CAS  Google Scholar 

  11. Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA et al (1999) Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet 22:175–177

    Article  PubMed  CAS  Google Scholar 

  12. Houten SM, van Woerden CS, Wijburg FA, Wanders RJ, Waterham HR (2003) Carrier frequency of the V377I (1129G>A) MVK mutation, associated with Hyper-IgD and periodic fever syndrome, in the Netherlands. Eur J Hum Genet 11:196–200

    Article  PubMed  CAS  Google Scholar 

  13. Kodell RL, Young JF, Delongchamp RR, Turturro A, Chen JJ, Gaylor DW, Howard PC, Zheng Q (2001) A mechanistic approach to modelling the risk of liver tumours in mice exposed to fumonisin B1 in the diet. Food Addit Contam 18:237–253

    Article  PubMed  CAS  Google Scholar 

  14. Lainka E, Neudorf U, Lohse P, Timmann C, Bielak M, Stojanov S, Huss K, von Kries R, Niehues T (2012) Incidence and clinical features of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) and spectrum of mevalonate kinase (MVK) mutations in German children. Rheumatol Int 32:3253–3260

    Article  PubMed  CAS  Google Scholar 

  15. Lee HR, Han TY, Son SJ, Lee JH (2011) Squamous cell carcinoma developing within lesions of disseminated superficial actinic porokeratosis. Ann Dermatol 23:536–538

    Article  PubMed  PubMed Central  Google Scholar 

  16. Leyva-Vega M, Weiss PF, Ganesh J, Conlin L, Spinner NB, Matthews RP (2011) Significant liver disease in a patient with Y116H mutation in the MVK gene. Am J Med Genet A 155A:1461–1464

    Article  PubMed  Google Scholar 

  17. Li JH, Yang ZH, Li B, Chen HD (2011) Squamous cell carcinoma arising from giant porokeratosis. Dermatol Surg 37:855–857

    PubMed  CAS  Google Scholar 

  18. Liu P, Zhang S, Yao Q, Liu X, Wang X, Huang C, Huang X, Wang P, Yuan M, Liu JY et al (2008) Identification of a genetic locus for autosomal dominant disseminated superficial actinic porokeratosis on chromosome 1p31.3-p31.1. Hum Genet 123:507–513

    Article  PubMed  CAS  Google Scholar 

  19. Luan J, Niu Z, Zhang J, Crosby ME, Zhang Z, Chu X, Wang Z, Huang W, Xiang L, Zheng Z (2011) A novel locus for disseminated superficial actinic porokeratosis maps to chromosome 16q24.1-24.3. Hum Genet 129:329–334

    Article  PubMed  Google Scholar 

  20. Mizuno T, Sakai H, Nishikomori R, Oshima K, Ohara O, Hata I, Shigematsu Y, Ishige T, Tamura K, Arakawa H (2012) Novel mutations of MVK gene in Japanese family members affected with hyperimmunoglobulinemia D and periodic fever syndrome. Rheumatol Int 32:3761–3764

    Article  PubMed  CAS  Google Scholar 

  21. Naruto T, Nakagishi Y, Mori M, Miyamae T, Imagawa T, Yokota S (2009) Hyper-IgD syndrome with novel mutation in a Japanese girl. Mod Rheumatol 19:96–99

    Article  PubMed  Google Scholar 

  22. Samkari A, Borzutzky A, Fermo E, Treaba DO, Dedeoglu F, Altura RA (2010) A novel missense mutation in MVK associated with MK deficiency and dyserythropoietic anemia. Pediatrics 125:e964–e968

    Article  PubMed  Google Scholar 

  23. Schena D, Papagrigoraki A, Frigo A, Girolomoni G (2010) Eruptive disseminated porokeratosis associated with internal malignancies: a case report. Cutis 85:156–159

    PubMed  Google Scholar 

  24. Scola N, Skrygan M, Wieland U, Kreuter A, Gambichler T (2012) Altered gene expression in squamous cell carcinoma arising from congenital unilateral linear porokeratosis. Clin Exp Dermatol 37:781–785

    Article  PubMed  CAS  Google Scholar 

  25. Sornsakrin M, Wenner K, Ganschow R (2009) B cell cytopenia in two brothers with hyper-IgD and periodic fever syndrome. Eur J Pediatr 168:825–831

    Article  PubMed  CAS  Google Scholar 

  26. Stojanov S, Lohse P, Lohse P, Hoffmann F, Renner ED, Zellerer S, Kéry A, Shin YS, Haas D, Hoffmann GF et al (2004) Molecular analysis of the MVK and TNFRSF1A genes in patients with a clinical presentation typical of the hyperimmunoglobulinemia D with periodic fever syndrome: a low-penetrance TNFRSF1A variant in a heterozygous MVK carrier possibly influences the phenotype of hyperimmunoglobulinemia D with periodic fever syndrome or vice versa. Arthritis Rheum 50:1951–1958

    Article  PubMed  CAS  Google Scholar 

  27. Takada K, Aksentijevich I, Mahadevan V, Dean JA, Kelley RI, Kastner DL (2003) Favorable preliminary experience with etanercept in two patients with the hyperimmunoglobulinemia D and periodic fever syndrome. Arthritis Rheum 48:2645–2651

    Article  PubMed  CAS  Google Scholar 

  28. Tahara M, Sakai H, Nishikomori R, Yasumi T, Heike T, Nagata I, Inui A, Fujisawa T, Shigematsu Y, Nishijima K et al (2011) Patient with neonatal-onset chronic hepatitis presenting with mevalonate kinase deficiency with a novel MVK gene mutation. Mod Rheumatol 21:641–645

    Article  PubMed  Google Scholar 

  29. Tas DA, Dinkci S, Erken E (2012) Different clinical presentation of the hyperimmunoglobulin D syndrome (HIDS) (four cases from Turkey). Clin Rheumatol 31:889–893

    Article  PubMed  Google Scholar 

  30. van der Hilst JC, Bodar EJ, Barron KS, Frenkel J, Drenth JP, van der Meer JW, Simon A, International HIDS Study Group (2008) Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Medicine (Baltimore) 87:301–310

    Article  Google Scholar 

  31. Vivas AC, Maderal AD, Kirsner RS (2012) Giant ulcerating squamous cell carcinoma arising from linear porokeratosis: a case study. Ostomy Wound Manage 58:18–20

    PubMed  Google Scholar 

  32. Wang P, Wei Z, Yan B, Huang T, Gou K, Dai Y, Zheng M, Wang M, Cheng X, Wang X et al (2012) Establishment of a transgenic mouse model with liver-specific expression of secretory immunoglobulin D. Sci China Life Sci 55:219–227

    Article  PubMed  CAS  Google Scholar 

  33. Wei S, Zhang TD, Zhou Y, Zhang XB, Zhu HL, Li J, Huang ZM, Deng L, Zhang XJ (2010) Fine mapping of the disseminated superficial porokeratosis locus to a 2.7 Mb region at 18p11.3. Clin Exp Dermatol 35:664–667

    Article  PubMed  CAS  Google Scholar 

  34. Xia JH, Yang YF, Deng H, Tang BS, Tang DS, He YG, Xia K, Chen SX, Li YX, Pan Q et al (2000) Identification of a locus for disseminated superficial actinic porokeratosis at chromosome 12q23.2-24.1. J Invest Dermatol 114:1071–1074

    Article  PubMed  CAS  Google Scholar 

  35. Zhang SQ, Jiang T, Li M, Zhang X, Ren YQ, Wei SC, Sun LD, Cheng H, Li Y, Yin XY et al (2012) Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis. Nat Genet 44:1156–1160

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by a grant from Nanfang Hospital (JQ201201) to Yan-Hua Liang.

Conflict of interests

The authors have declared that no competing interests exist.

Author information

Authors and Affiliations

  1. Department of Dermatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, Guangdong, China

    Kang Zeng, Qi-Guo Zhang, Li Li, Yan Duan & Yan-Hua Liang

Authors
  1. Kang Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qi-Guo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan-Hua Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yan-Hua Liang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zeng, K., Zhang, QG., Li, L. et al. Splicing mutation in MVK is a cause of porokeratosis of Mibelli. Arch Dermatol Res 306, 749–755 (2014). https://doi.org/10.1007/s00403-014-1465-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-014-1465-7

Keywords

Search

Navigation