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Original article
3q27.3 microdeletional syndrome: a recognisable clinical entity associating dysmorphic features, marfanoid habitus, intellectual disability and psychosis with mood disorder
  1. Julien Thevenon1,2,
  2. Patrick Callier2,3,
  3. Hélène Poquet4,
  4. Iben Bache5,
  5. Bjorn Menten6,
  6. Valérie Malan7,
  7. Maria Luigia Cavaliere8,
  8. Jean-Paul Girod4,
  9. Christel Thauvin-Robinet1,2,
  10. Salima El Chehadeh1,
  11. Jean-Michel Pinoit4,
  12. Frederic Huet9,
  13. Bruno Verges10,
  14. Jean-Michel Petit10,
  15. Anne-Laure Mosca-Boidron2,3,
  16. Nathalie Marle2,3,
  17. Francine Mugneret3,
  18. Alice Masurel-Paulet1,
  19. Antonio Novelli11,
  20. Zeynep Tümer12,
  21. Bart Loeys13,
  22. Stanislas Lyonnet14,
  23. Laurence Faivre1,2
  1. 1Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, CHU de Dijon, Dijon, France
  2. 2Université de Bourgogne, EA4271 GAD, Dijon, France
  3. 3Laboratoire de Cytogénétique, CHU Dijon, Dijon, France
  4. 4Service de Pédopsychiatrie, Hôpital d'Enfants, CHU Dijon, Dijon, France
  5. 5Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark
  6. 6Center for Medical Genetics, Ghent University Hospital & Ghent University, Ghent, Belgium
  7. 7INSERM U 781 & Département de Génétique, Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris, France
  8. 8Medical Genetics, Azienda Ospedaliera “A. Cardarelli”, Naples, Italy
  9. 9Service de Pédiatrie 1, CHU de Dijon, Dijon, France
  10. 10Centre Hospitalier Universitaire de Dijon, Hôpital du Bocage, Service d'Endocrinologie, Diabète et Maladies métaboliques, Dijon, France
  11. 11Mendel Laboratory,Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Rome, Italy
  12. 12The Kennedy Center, Glostrup, Denmark
  13. 13Department of Medical Genetics, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium
  14. 14Université Paris Descartes—Sorbonne Paris Cité, Institut Imagine, et INSERM U-781, AP-HP Hôpital Necker-Enfants Malades, Paris, France
  1. Correspondence to Professor Laurence Faivre, Centre de Génétique, Hôpital d'Enfants, 10 bd Maréchal de Lattre de Tassigny, Dijon Cedex 21034, France; laurence.faivre{at}chu-dijon.fr

Abstract

Background Since the advent of array-CGH, numerous new microdeletional syndromes have been delineated while others remain to be described. Although 3q29 subtelomeric deletion is a well-described syndrome, there is no report on 3q interstitial deletions.

Methods We report for the first time seven patients with interstitial deletions at the 3q27.3q28 locus gathered through the Decipher database, and suggest this locus as a new microdeletional syndrome.

Results The patients shared a recognisable facial dysmorphism and marfanoid habitus, associated with psychosis and mild to severe intellectual disability (ID). Most of the patients had no delay in gross psychomotor acquisition, but had severe impaired communicative and adaptive skills. Two small regions of overlap were defined. The first one, located on the 3q27.3 locus and common to all patients, was associated with psychotic troubles and mood disorders as well as recognisable facial dysmorphism. This region comprised several candidate genes including SST, considered a candidate for the neuropsychiatric findings because of its implication in interneuronal migration and differentiation processes. A familial case with a smaller deletion allowed us to define a second region of overlap at the 3q27.3q28 locus for marfanoid habitus and severe ID. Indeed, the common morphological findings in the first four patients included skeletal features from the marfanoid spectrum: scoliosis (4/4), long and thin habitus with leanness (average Body Mass Index of 15 (18.5<N<25)) (4/4), arachnodactyly (3/4) and pectus excavatum (2/4)). This phenotype could be explained by the deletion of the AHSG gene, which encodes a secreted protein implicated in bone maturation and the TGFb signalling pathway.

Conclusions We report on a new microdeletional syndrome that associates with a recognisable facial dysmorphism and marfanoid habitus including scoliosis, neuropsychiatric disorders of the psychotic spectrum and moderate to severe ID.

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