Bathing suit ichthyosis

ARTICLE

Auteur(s) : Felicidade Trindade¹, Teresa Fiadeiro², Antonio Torrelo³, Hans Christian Hennies⁴, Ingrid Hausser⁵, Heiko Traupe⁶

¹Department of Dermatology, Hospital de Cascais, Av. Brigadeiro Victor Novais Gonçalves, 2755-009 Cascais, Portugal
²Department of Dermatology, Hospital da Luz, Lisbon, Portugal
³Department of Dermatology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
⁴Cologne Center for Genomics, Division of Dermatogenetics, University of Cologne, Germany
⁵Department of Dermatology, University of Heidelberg, Germany
⁶Department of Dermatology, University of Muenster, Germany

accepté le 18 F�vrier 2010

Bathing suit ichthyosis (BSI) is a rare and unique clinical form of autosomal recessive congenital ichthyosis [1]. It is characterized by dark-grey or brownish scaling restricted to the “bathing suit” areas, whereas the extremities and central face are almost completely spared. Recently, it has been demonstrated to be a temperature-sensitive phenotype, which is caused by specific transglutaminase-1 (TGase-1) gene mutations leading to protein dysfunction in higher temperature conditions [2].

Case report

Ultrastructural analyses were performed on the affected and unaffected skin. Affected skin revealed groups of single polygonal clefts representing remnants of cholesterol crystals within the thickened massive horny layer (figure 3A). The unaffected skin of the arm showed a normal ultrastructure and a normal diameter of the stratum corneum (figure 3B).

We performed a biochemical in situ test for the TGase-1 enzyme activity: cryosections of 3-4 μm were blocked with 1% bovine serum albumin in phosphate-buffered saline for 30 min and directly incubated with 0.1 mM TGase substrate biotinyl cadaverine (Molecular Probes, Leiden, The Netherlands), which is incorporated into the cornified cell envelope in the presence of calcium ions (5 mM). At physiological pH 7.4 (100 mM Tris-HCl) this reaction is almost exclusively performed by TGase-1 (reaction time 90 min). Incubation with 5 mM EDTA served as negative control. The incorporated biotinylated substrate was incubated with fluorochrome-coupled streptavidin 1:100 (Jackson ImmunoResearch Laboratoires Inc., West Grove, PA, USA).

In affected skin there was a complete lack of the normal pericellular TGase-1 signal in the stratum granulosum (figure 4A), while some non-specific TGase activity could be noted in the stratum corneum. In contrast, there was a normal pattern of TGase-1 activity in unaffected skin (figure 4B).

EDTA blood was collected from the patient. DNA was extracted from peripheral blood leukocytes using standard procedures. The translated exons 2-15 of TGase-1 gene (TGM1) were amplified by polymerase chain reaction. A homozygous mutation was identified in exon 6 of the TGase-1 gene (TGM1). The mutation at nucleotide c.944 converts an arginine residue to leucine, designated as p.R315L [3].

The patient was treated with emollients, and by the age of 4 years she developed scaling on the elbow fossae and popliteal areas.

Discussion

BSI was initially described in South African patients [1], but has also been reported in Caucasian individuals from Europe and the Mediterranean area (Germany, Netherlands, France, Turkey and Morocco) [2] totalizing 18 patients in the literature. Two patients had a history of consanguinity. Moreover, all 8 patients from South Africa had the same mutation, p.R315L, pointing to a founder effect in this group of patients. Seven of these belong to the Nguni ethnic groups (Zulu, Swazi, and Xhosa) [5]. Interestingly, our patient showed the same homozygous mutation, but she was from Guinea and did not belong to any of these ethnic groups.

Loss or drastic reduction of TGase-1 function leads to defective cornified cell envelope formation and collapse of the stratum corneum lipid barrier [6]. TGase-1 activity was shown to be differentially present in unaffected and affected skin in BSI. In unaffected skin TGase1 shows a normal in situ activity and affected skin reveals a residual cytoplasmic enzyme activity (table 1). Furthermore, comparing the ultrastructural features of affected and unaffected skin, the cholesterol clefts associated with TGase-1 deficiency were seen in affected skin but not in normal skin (table 1) [2].

Sequencing analyses in BSI patients have revealed homozygous or compound heterozygous TGM1 mutations in 14 cases reported so far (table 1) [2, 5]. In African individuals from South Africa as well as in our patient from Guinea the same mutation was detected in exon 6 of TGM1, a homozygous G>T transversion at nucleotide c.944, thus suggesting a founder effect. Oji et al. suggested that skin temperature might play a role for the development of BSI. Digital thermography showed a striking correlation between warmer body areas and the presence of scaling [2]. Aufenvenne et al. compared the TGase-1 activity of 8 BSI cases with 3 cases of generalized lamellar ichthyosis and showed that BSI mutations exhibit a decreased enzyme activity and a marked shift in temperature optimum from 37 °C for normal (“wild type”) TGase-1 to 31 °C (BSI-mutation TGase-1), explaining the clinical phenotype with the unaffected areas on the central face, arms and legs having a lower body temperature [7].
Table 1 Summary of the BSI cases reported in the literature

Acknowledgements

References

2 Oji V, Hautier JM, Ahvazi B, et al. Bathing suit ichthyosis is caused by transglutaminase -1 deficiency: evidence for a temperature-sensitive phenotype. Hum Mol Genet 2006; 15: 3083-97.

3 Tok J, Garzon MC, Cserhalmi-Friedman P, Lam HM, Spitz JL, Christiano AM. Identification of mutations in the transglutaminase 1 gene in lamellar ichthyosis. Exp Dermatol 1999; 8: 128-33.

4 Oji V, Tadini G, Akiyama M, et al. Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009. J Am Acad Dermatol 2010; in press.

5 Arita K, Jacyk WK, Wessagowit V, et al. The South African “bathing suit ichthyosis” is a form of lamellar ichthyosis caused by a homozygous missense mutation, p.R315L, in transglutaminase 1. J Invest Dermatol 2007; 127: 490-3.

6 Elias PM, Schmuth M, Uchida Y, et al. Basis for abnormal desquamation and permeability in lamellar ichthyosis. Exp Dermatol 2002; 11: 248-56

7 Aufenvenne K, Oji V, Walker T, et al. Transglutaminase-1 and Bathing Suit Ichthyosis: Molecular Analysis of Gene/Environment Interactions. J Invest Dermatol 2009; 129: 2068-71.