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Molekulare und genetische Aspekte der idiopathischen Skoliose

Bluttest bei idiopathischer Skoliose

Molecular and genetic aspects of idiopathic scoliosis

Blood test for idiopathic scoliosis

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Zusammenfassung

Wirbelsäulendeformitäten und insbesondere die Skoliose sind die häufigsten orthopädischen Deformitäten bei Kindern und Jugendlichen. Etwa 1–6% der Bevölkerung haben eine Skoliose. Diese Erkrankung führt zu schweren Deformitäten der Wirbelsäule und betrifft vorwiegend jugendliche Mädchen.

Obgleich die multifaktorielle Genese der adoleszenten idiopathischen Skoliose (AIS) allgemein anerkannt ist, sind die genetischen Ursachen der AIS noch weitgehend unbekannt. Unsere vorherigen Studien deuten auf eine generalisierte Funktionsstörung bei der Übertragung von Melatonin (Hormon, das hauptsächlich im Gehirn und in der Epiphyse produziert wird). Mittlerweile haben wir nachgewiesen, dass ein derartiger Defekt in der Signalübertragung durch chemische Veränderungen verursacht wird, die die Funktion der an die Melatoninrezeptoren gekoppelten hemmenden G-Proteine inaktivieren. Diese Entdeckung hat zur Entwicklung des ersten Bluttests zur Erkennung von symptomlosen Kindern geführt, bei denen das Risiko einer Skoliose besteht. Da eine Funktion bestimmt wird (Zellreaktion auf Melatonin), hat dieser Test den einzigartigen Vorteil ohne Kenntnisse von Mutationen in defekten Genen, die eine AIS auslösen können, durchgeführt werden zu können.

Abstract

Spinal deformities, and particularly scoliosis, are the most frequent forms of orthopedic deformities in children and adolescents. About 1–6% of the population has scoliosis. This disorder leads to severe spinal deformities and predominantly affects adolescent girls.

Although the multifactorial origin of adolescent idiopathic scoliosis (AIS) is broadly recognized, the genetic causes of AIS are still largely unknown. Our previous studies suggested a generalized dysfunction of melatonin transduction (the hormone that is primarily produced in the brain and epiphysis). In the meantime we have demonstrated that such a defect of signal transduction is caused by chemical alterations, which inactivate the function of the inhibitory G protein-coupled melatonin receptors. This discovery has led to the development of the first blood test to detect children without symptoms who are at risk of developing scoliosis. Since a single function (cellular reaction to melatonin) is determined, the unique advantage of this test is that it can be performed without knowledge of mutations in defective genes that could provoke the onset of AIS.

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Danksagung

Unterstützt durch Forschungsstipendien von La Fondation Yves Cotrel de l’Institut de France, Paris, Frankreich (Prof. Moreau und Dr. Labelle) und von Paradigm Spine, New York, USA (Prof. Moreau). Hr. Azeddine wird von einem Promotionsstipendium eines Mentoren-Schulungsprogramms bzw. von einem Forschungsprogramm des Canadian Institute of Health unterstützt. Wir sind den Studienteilnehmern und ihren Familien zu Dank verpflichtet. Wir danken außerdem Fr. Ginette Lacroix für die Studienkoordination, Fr. Ginette Larouche, Fr. Marjolaine Roy-Beaudry und Fr. Julie Joncas für ihre pflegerische Unterstützung sowie den Pflegeteams am Sainte-Justine University Hospital, The Montreal’s Children Hospital und The Shriners Hospital for Children in Montreal.

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehung hin: Paradigm Spine beteiligt sich an Forschungsarbeiten von Prof. Moreau. Trotz des möglichen Interessenkonflikts ist der Beitrag unabhängig und produktneutral.

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Authors and Affiliations

  1. Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital Research Center, Université de Montreal, Côte-Sainte-Catherine Road, 3175, Montreal, Québec, Canada

    A. Moreau Ph.D., M.-Y. Akoumé Ndong, B. Azeddine, A. Franco, I. Turgeon & D. Wang

  2. Department of Stomatology, Faculty of Dentistry, Université de Montreal, Montreal, Canada

    A. Moreau Ph.D., P.H. Rompré & F. Moldovan

  3. Department of Biochemistry, Faculty of Medicine, Université de Montreal, Montreal, Canada

    A. Moreau Ph.D. & M.-Y. Akoumé Ndong

  4. Sainte-Justine University Hospital Research Center and Department of Social Medicine and Prevention, Université de Montreal, Montreal, Canada

    M.-H. Roy-Gagnon

  5. Department of Surgery, University of Alberta, Edmonton, Canada

    K.M. Bagnall

  6. Orthopedic Division, Sainte-Justine University Hospital and Department of Surgery, Université de Montreal, Montreal, Canada

    B. Poitras, H. Labelle, C.-H. Rivard, G. Grimard & S. Parent

  7. Orthopedic Division, The Montreal Children’s Hospital, McGill University, Montreal, Canada

    J. Ouellet

  8. Laboratory of Molecular Orthopedics, Sainte-Justine Hospital Reseach Center, Montreal, Canada

    F. Moldovan

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  1. A. Moreau Ph.D.
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  2. M.-Y. Akoumé Ndong
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  3. B. Azeddine
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  4. A. Franco
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  5. P.H. Rompré
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  6. M.-H. Roy-Gagnon
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  8. D. Wang
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  9. K.M. Bagnall
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  10. B. Poitras
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  11. H. Labelle
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  14. J. Ouellet
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  15. S. Parent
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  16. F. Moldovan
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Correspondence to A. Moreau Ph.D..

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Moreau, A., Akoumé Ndong, MY., Azeddine, B. et al. Molekulare und genetische Aspekte der idiopathischen Skoliose. Orthopäde 38, 114–121 (2009). https://doi.org/10.1007/s00132-008-1362-x

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