1. bookVolume 24 (2016): Issue 4 (December 2016)
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
access type Open Access

NIPAL4 mutation c.527C˃A identified in Romanian patients with autosomal recessive congenital ichthyosis

Published Online: 30 Dec 2016
Page range: 387 - 398
Received: 07 Jun 2016
Accepted: 21 Sep 2016
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
Abstract

Introduction: Autosomal recessive congenital ichthyosis is a non-syndromic ichthyosis, with a genetic background of mutations in 9 genes. This case series presents clinical and paraclinical particularities of 3 Romanian ARCI patients with NIPAL4 mutation c.527C>A.

Material and methods: Three Caucasian patients were investigated, two sisters and an unrelated female patient, aged 47, 49, and 42 respectively. Skin anomalies were recorded and documented photographically; peripheral blood samples were harvested for DNA extraction and gene analysis. Skin biopsies were used for histological assessment, electron microscopy, and evaluation of in situ transglutaminase 1 activity.

Results: All patients presented with generalized ichthyosis, palmoplantar keratoderma, normal hair shafts, and significant oral manifestations. Natural evolution was relatively stable in all cases, without phenotype changing. Medical treatment with retinoids in patients 1 and 2 resulted in normalisation of the skin condition.

Histological samples showed hyperkeratosis, acanthosisand perivascular inflammatory infiltrates in the dermis. Positive findings of transglutaminase 1 in situ activity excluded TGM1 deficiency. Direct sequencing of amplicons revealed one homozygous mutation in exon 4, a c.527C>A missense mutation.

Conclusions: This is the first report of the hotspot mutation NIPAL4 c.527C>A in Romanian autosomal recessive congenital ichthyosis patients. The phenotype was similar to that reported in the literature, while transglutaminase 1 activity in situ assay detected differences in enzyme distribution between patients bearing the same mutation but different phenotypes. Based on the current data, NIPAL4 mutations are more frequent than TGM1 mutations in Romanian patients with autosomal recessive congenital ichthyosis.

Keywords

1. Dreyfus I, Chouquet C, Ezzedine K, Henner S, Chiaverini C, Maza A, et al. Prevalence of inherited ichthyosis in France: a study using capture-recapture method. Orphanet J Rare Dis. 2014;9:1. DOI: 10.1186/1750-1172-9-1.10.1186/1750-1172-9-1389203724393603Search in Google Scholar

2. Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E, et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009. J Am Acad Dermatol. 2010;63(4):607-41. DOI: 10.1016/j.jaad.2009.11.020.10.1016/j.jaad.2009.11.02020643494Search in Google Scholar

3. Akiyama M, Sawamura D, Shimizu H. The clinical spectrum of nonbullous congenital ichthyosi-form erythroderma and lamellar ichthyosis. Clin Exp Dermatol. 2003;28(3):235-40. DOI: 10.1046/j.1365-2230.2003.01295.x.10.1046/j.1365-2230.2003.01295.x12780701Search in Google Scholar

4. Traupe H, Fischer J, Oji V. Nonsyndromic types of ichthyoses - an update. J Dtsch Dermatol Ges. 2014;12(2):109-21. DOI: 10.1111/ddg.12229 DOI: 10.1111/ddg.12229_suppl.10.1111/ddg.1222924119255Search in Google Scholar

5. Lefevre C, Bouadjar B, Karaduman A, Jobard F, Saker S, Ozguc M, et al. Mutations in ichthyin a new gene on chromosome 5q33 in a new form of auto-somal recessive congenital ichthyosis. Hum Mol Genet. 2004;13(20):2473-82. DOI: 10.1093/hmg/ddh263.10.1093/hmg/ddh26315317751Search in Google Scholar

6. Quamme GA. Molecular identification of ancient and modern mammalian magnesium transporters. Am J Physiol Cell Physiol. 2010;298(3):C407-29. DOI: 10.1152/ajpcell.00124.2009.10.1152/ajpcell.00124.200919940067Search in Google Scholar

7. Li H, Vahlquist A, Torma H. Interactions between FATP4 and ichthyin in epidermal lipid processing may provide clues to the pathogenesis of autosomal recessive congenital ichthyosis. J Dermatol Sci. 2013;69(3):195-201. DOI: 10.1016/j.jdermsci.2012.11.593.10.1016/j.jdermsci.2012.11.59323290633Search in Google Scholar

8. Fischer J. Autosomal recessive congenital ichthyosis. J Invest Dermatol. 2009;129(6):1319-21. DOI: 10.1038/jid.2009.57.10.1038/jid.2009.5719434086Search in Google Scholar

9. Dahlqvist J, Klar J, Hausser I, Anton-Lamprecht I, Pigg MH, Gedde-Dahl T, Jr., et al. Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis. J Med Genet. 2007;44(10):615-20. DOI: 10.1136/jmg.2007.050542.10.1136/jmg.2007.050542259797017557927Search in Google Scholar

10. Wajid M, Kurban M, Shimomura Y, Christiano AM. NIPAL4/ichthyin is expressed in the granular layer of human epidermis and mutated in two Pakistani families with autosomal recessive ichthyosis. Dermatology. 2010;220(1):8-14. DOI: 10.1159/000265757.10.1159/000265757285527620016120Search in Google Scholar

11. Maier D, Mazereeuw-Hautier J, Tilinca M, Cosgarea R, Jonca N. Novel mutation in NIPAL4 in a Romanian family with autosomal recessive congenital ichthyosis. Clin Exp Dermatol. 2016 Apr;41(3):279-82.10.1111/ced.1274026456858Search in Google Scholar

12. Alavi A, Shahshahani MM, Klotzle B, Fan JB, Ronaghi M, Elahi E. Manifestation of diffuse yellowish keratoderma on the palms and soles in autosomal recessive congenital ichthyosis patients may be indicative of mutations in NIPAL4. The Journal of dermatology. 2012;39(4):375-81. DOI: 10.1111/j.1346-8138.2011.01412.x.10.1111/j.1346-8138.2011.01412.x22098531Search in Google Scholar

13. Israeli S, Goldberg I, Fuchs-Telem D, Bergman R, Indelman M, Bitterman-Deutsch O, et al. Nonsyndromic autosomal recessive congenital ichthyosis in the Israeli population. Clin Exp Dermatol. 2013;38(8):911-6. DOI: 10.1111/ced.12148.10.1111/ced.1214823621129Search in Google Scholar

14. Raghunath M, Hennies HC, Ahvazi B, Vogel M, Reis A, Steinert PM, et al. Self-healing collodion baby: a dynamic phenotype explained by a particular transglutaminase-1 mutation. J Invest Dermatol. 2003;120(2):224-8. DOI: 10.1046/j.1523-1747.2003.12032.x.10.1046/j.1523-1747.2003.12032.x12542526Search in Google Scholar

15. Farasat S, Wei MH, Herman M, Liewehr DJ, Steinberg SM, Bale SJ, et al. Novel transglutaminase-1 mutations and genotype-phenotype investigations of 104 patients with autosomal recessive congenital ichthyosis in the USA. J Med Genet. 2009;46(2):103-11. DOI: 10.1136/jmg.2008.060905.10.1136/jmg.2008.060905304448118948357Search in Google Scholar

16. Eckl KM, de Juanes S, Kurtenbach J, Natebus M, Lugassy J, Oji V, et al. Molecular analysis of 250 patients with autosomal recessive congenital ichthyosis: evidence for mutation hotspots in ALOXE3 and allelic heterogeneity in ALOX12B. J Invest Dermatol. 2009;129(6):1421-8. DOI: 10.1038/jid.2008.409.10.1038/jid.2008.40919131948Search in Google Scholar

17. Haenssle HA, Finkenrath A, Hausser I, Oji V, Traupe H, Hennies HC, et al. Effective treatment of severe thermodysregulation by oral retinoids in a patient with recessive congenital lamellar ichthyosis. Clin Exp Dermatol. 2008;33(5):578-81. DOI: 10.1111/j.1365-2230.2008.02709.x.10.1111/j.1365-2230.2008.02709.x18355358Search in Google Scholar

18. Vahlquist A, Bygum A, Ganemo A, Virtanen M, Hellstrom-Pigg M, Strauss G, et al. Genotypic and clinical spectrum of self-improving collodion ichthyosis: ALOX12B, ALOXE3, and TGM1 mutations in Scandinavian patients. J Invest Dermatol. 2010;130(2):438-43. DOI: 10.1038/jid.2009.346.10.1038/jid.2009.34619890349Search in Google Scholar

19. Pavez Lorie E, Ganemo A, Borgers M, Wouters L, Blockhuys S, van de Plassche L, et al. Expression of retinoid-regulated genes in lamellar ichthyosis vs. healthy control epidermis: changes after oral treatment with liarozole. Acta Derm Venereol. 2009;89(1):12-20. DOI: 10.2340/00015555-0573.10.2340/00015555-057319197536Search in Google Scholar

20. Halusic AM, Sepich VR, Shirley DC, Granjeiro JM, Costa MC, Kuchler EC, et al. Calcium and magnesium levels in primary tooth enamel and genetic variation in enamel formation genes. Pediatr Dent. 2014;36(5):384-8.Search in Google Scholar

21. Li H, Lorie EP, Fischer J, Vahlquist A, Torma H. The expression of epidermal lipoxygenases and transglutaminase-1 is perturbed by NIPAL4 mutations: indications of a common metabolic pathway essential for skin barrier homeostasis. J Invest Dermatol. 2012;132(10):2368-75. DOI: 10.1038/jid.2012.160.10.1038/jid.2012.16022622417Search in Google Scholar

22. Pigg M, Gedde-Dahl T, Jr., Cox D, Hausser I, Anton-Lamprecht I, Dahl N. Strong founder effect for a transglutaminase 1 gene mutation in lamellar ichthyosis and congenital ichthyosiform erythroderma from Norway. Eur J Hum Genet. 1998;6(6):589-96. DOI: 10.1038/sj.ejhg.5200224.10.1038/sj.ejhg.52002249887377Search in Google Scholar

23. Dahlqvist J, Westermark GT, Vahlquist A, Dahl N. Ichthyin/NIPAL4 localizes to keratins and desmosomes in epidermis and Ichthyin mutations affect epidermal lipid metabolism. Arch Dermatol Res. 2012;304(5):377-86. DOI: 10.1007/s00403-012-1207-7.10.1007/s00403-012-1207-722258272Search in Google Scholar

24. Maier D, Tilinca M, Cosgarea R. Detection of in situ Transglutaminase 1 activity in Romanian patients with autosomal recessive congenital ichthyosis. Annals of RSCB. 2014;19(1):65-72.Search in Google Scholar

25. Rodriguez-Pazos L, Ginarte M, Fachal L, Toribio J, Carracedo A, Vega A. Analysis of TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 in autosomal recessive congenital ichthyosis from Galicia (NW Spain): evidence of founder effects. Br J Dermatol. 2011;165(4):906-11. DOI: 10.1111/j.1365-2133.2011.10454.x.10.1111/j.1365-2133.2011.10454.x21668430Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo