Etienne Berard

Publications (2)9.7 Total impact

• Source

  Available from: Kazumasa Wakamatsu

  Article: Cystinosin is a melanosomal protein that regulates melanin synthesis.

  Christine Chiaverini, Laura Sillard, Enrica Flori, Shosuke Ito, Stefania Briganti, Kazumasa Wakamatsu, Eric Fontas, Etienne Berard, Mathilde Cailliez, Pierre Cochat, Michel Foulard, Geneviève Guest, Patrick Niaudet, Mauro Picardo, François-Xavier Bernard, Corinne Antignac, Jean Paul Ortonne, Robert Ballotti
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  ABSTRACT: Cystinosis is a rare autosomal recessive disease characterized by cystine crystal accumulation leading to multiorgan dysfunctions and caused by mutation in CTNS. CTNS encodes cystinosin, a cystine/H(+) symporter that exports cystine out of the lysosomes. Patients with cystinosis frequently exhibit blond hair and fair complexion, suggesting an alteration in melanogenesis. However, the pigmentation singularities of these patients have not been studied, and the role of cystinosin in melanogenesis has remained unknown. In our study, a clinical evaluation of 27 patients with cystinosis showed that 44% had a cutaneous pigmentation dilution compared to their relatives. Analysis of the hair melanin content in these patients by HPLC demonstrated a 50% decrease in eumelanin (4360 vs. 9360 ng/mg), and a 2-fold increase in pheomelanin (53 vs. 20 ng/mg), the yellow/red pigments. Cystinosin-deficient mice also showed a 4-fold increase in hair pheomelanin content. In vitro studies showed that cystinosin was located at melanosomes. CTNS silencing led to a 75% reduction of melanin synthesis that was caused by a degradation of tyrosinase by lysosomal proteases. Our results objectify the pigmentation defect in patients with cystinosis. We also identify the role of CTNS in melanogenesis and add a new gene to the list of the genes involved in the control of skin and hair pigmentation.
  The FASEB Journal 05/2012; 26(9):3779-89. · 5.71 Impact Factor
• Article: In vivo reflectance confocal microscopy of the skin: A noninvasive means of assessing body cystine accumulation in infantile cystinosis.

  Christine Chiavérini, Hee-Young Kang, Laura Sillard, Etienne Berard, Patrick Niaudet, Geneviève Guest, Mathilde Cailliez, Philippe Bahadoran, Jean Philippe Lacour, Robert Ballotti, Jean Paul Ortonne
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  ABSTRACT: BACKGROUND: Patients with infantile nephropathic cystinosis have progressive accumulation of cystine in tissues leading to delayed extrarenal complications. No simple tool is available to evaluate the level of body cystine accumulation. OBJECTIVE: We sought to determine the value of in vivo reflectance confocal microscopy of the skin in patients with infantile nephrogenic cystinosis. METHODS: Nine patients and control subjects were recruited for this study. Images were acquired by means of a near-infrared reflectance confocal laser scanning microscope. RESULTS: Scattered bright particles within the papillary dermis were observed in all patients but not in control subjects. The density of particles ranged from numerous (+++) to very few (+/-) and their distribution was heterogeneous. Electron microscopy confirmed that these particles corresponded to cystine crystal deposits within dermal fibroblasts. The density of cystine crystals within the dermis was greater in older patients, in patients with a high leukocyte cystine concentration, and with delayed cysteamine therapy. There was no correlation between the density of cystine deposits and renal disease or hypopigmentation but high levels of deposition occurred in association with extrarenal manifestations. LIMITATIONS: This is a preliminary study on a small sample of patients. Repeated examination and longer follow-up is necessary. CONCLUSION: In vivo reflectance confocal microscopy of the skin appears to be a noninvasive means of assessing body cystine accumulation in infantile cystinosis and could be used as a complementary marker of treatment response in addition to leukocyte cystine measurement.
  Journal of the American Academy of Dermatology 09/2011; · 3.99 Impact Factor