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The Spectrum of Niemann-Pick Type C Disease in Greece

  • Irene Mavridou
  • Evangelia Dimitriou
  • Marie T. Vanier
  • Lluisa Vilageliu
  • Daniel Grinberg
  • Philippe Latour
  • Athina Xaidara
  • Lilia Lycopoulou
  • Sevasti Bostantjopoulou
  • Dimitrios Zafeiriou
  • Helen MichelakakisEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 36)

Abstract

Niemann-Pick type C disease (NPC) is a neurovisceral lysosomal storage disease caused by mutations in either the NPC1 or the NPC2 gene. It is a cellular lipid trafficking disorder characterized by the accumulation of unesterified cholesterol and various sphingolipids in the lysosomes and late endosomes, and it exhibits a broad clinical spectrum. Today, over 420 disease-causing mutations have been identified in the NPC1 and the NPC2 genes. We present the clinical, biochemical, and molecular findings in 14 cases diagnosed in Greece during the last 28 years. Age at diagnosis ranged from 2.5 months to 48 years. Systemic manifestations were present in 7/14 patients. All developed neurological manifestations (age of onset 5 months to 42 years). Six patients are still alive (age: 5–50 years). Classical filipin staining pattern was observed in all but four patients (3 NPC1, 1 NPC2). The rate of LDL-induced cholesteryl ester formation was severely reduced in 4/7 and significantly reduced in 3/7 patients studied. Increased chitotriosidase activity was observed in 9/12 patients. Mutation analysis in 11 unrelated patients identified 12 different mutations in the NPC1 gene: eight previously described p.E1089K (c.3265G>A), p.F284Lfs*26 (c.852delT), p.A1132P(c.3394G>C), del promoter region and exons 1-10, p.R1186H (c.3557G>A), p.P1007A (c.3019C>G), p.Q92R(c.275A>G),p.S940L (c.2819C>T), and four novel ones: (p.N701K fs*13 (c.2102-2103insA), p.K1057R (c.3170A>G), IVS23+3insT(c.3591+3insT), p.C1119*(c.3357T>C); and the previously described IVS2+5G>A(c.190+5G>A) mutation in the NPC2 gene. All patients were of Greek origin. Assuming a birth rate of 100,000/year, a rough incidence estimate for NPC disease in Greece would be 0.5/100,000 births.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Irene Mavridou
    • 1
  • Evangelia Dimitriou
    • 1
  • Marie T. Vanier
    • 2
  • Lluisa Vilageliu
    • 3
  • Daniel Grinberg
    • 3
  • Philippe Latour
    • 2
  • Athina Xaidara
    • 4
  • Lilia Lycopoulou
    • 4
  • Sevasti Bostantjopoulou
    • 5
  • Dimitrios Zafeiriou
    • 6
  • Helen Michelakakis
    • 1
    Email author
  1. 1.Department Enzymology and Cellular FunctionInstitute of Child HealthAthensGreece
  2. 2.Laboratoire Gillet-Mérieux et Neurogénétique Moléculaire, Groupe Hospitalier EstHospices Civils de LyonLyonFrance
  3. 3.Department of GeneticsUniversity of Barcelona, CIBERER, IBUBBarcelonaSpain
  4. 4.1st Department Pediatrics University of AthensAghia Sofia Children’s HospitalAthensGreece
  5. 5.3rd University Department of NeurologyAristotle University of ThessalonikiThessalonikiGreece
  6. 6.1st Department PediatricsAristotle UniversityThessalonikiGreece

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