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  • A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features

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Original article
A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features
  1. A-M Molin1,
  2. J Andrieux2,
  3. D A Koolen3,
  4. V Malan4,
  5. M Carella5,
  6. L Colleaux4,
  7. V Cormier-Daire4,
  8. A David6,
  9. N de Leeuw3,
  10. B Delobel7,
  11. B Duban-Bedu7,
  12. R Fischetto8,
  13. F Flinter9,
  14. S Kjaergaard10,
  15. F Kok11,
  16. A C Krepischi12,13,
  17. C Le Caignec6,14,
  18. C Mackie Ogilvie15,
  19. S Maia16,
  20. M Mathieu-Dramard17,
  21. A Munnich4,
  22. O Palumbo5,
  23. F Papadia8,
  24. R Pfundt3,
  25. W Reardon18,
  26. A Receveur19,
  27. M Rio4,
  28. L Ronsbro Darling20,
  29. C Rosenberg12,
  30. J Sá16,
  31. L Vallee21,
  32. C Vincent-Delorme22,
  33. L Zelante5,
  34. M-L Bondeson1,
  35. G Annerén1
  1. 1Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
  2. 2Institut de Génétique Médicale, Hopital Jeanne de Flandre, CHRU de Lille, France
  3. 3Department of Human Genetics, Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
  4. 4Département de Génétique et INSERM U781, Université Paris Descartes, Hôpital, Necker-Enfants Malades, Paris, France
  5. 5Medical Genetics Unit IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
  6. 6CHU Nantes, Service de genetique medicale, Nantes, France
  7. 7Centre de Génétique Chromosomique, GHICL, Lille, France
  8. 8Unità Operativa Malattie Metaboliche Genetica Medica, P.O. Giovanni XXIII, A.O.U. Policlinico Consorziale, Bari, Italy
  9. 9Department of Clinical Genetics, Guy's & St Thomas' NHS Foundation Trust, London, UK
  10. 10Department of Clinical Genetics, University Hospital, Rigshospitalet, Copenhagen, Denmark
  11. 11Department of Neurology, Academic Hospital, University of São Paulo, Brazil
  12. 12Department of Evolutionary Biology, Institute of Biosciences, University of São Paulo, Brazil
  13. 13A.C. Camargo Hospital, São Paulo, Brazil
  14. 14Inserm, UMR_S915, l'institut du thorax, Nantes, France
  15. 15Department of Cytogenetics, Guy's & St Thomas' NHS Foundation Trust, London
  16. 16Serviço de Genética Médica, Centro Hospitalar de Coimbra, Coimbra, Portugal
  17. 17Service de Génétique Clinique, CHU d'Amiens, France
  18. 18Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland
  19. 19Laboratoire de Cytogénétique, CHU d'Amiens, France
  20. 20Rigshospitalet & Roskilde, Departments of Paediatrics, Denmark
  21. 21Service de Neuropédiatrie, CHRU de Lille, France
  22. 22Service de Génétique Médicale, Hôpital Jeanne de Flandre, CHRU de Lille, France
  1. Correspondence to Dr Anna-Maja Molin, Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Science for Life Laboratory, Uppsala 75237, Sweden; anna-maja.nystrom{at}slu.se

Abstract

Background Congenital deletions affecting 3q11q23 have rarely been reported and only five cases have been molecularly characterised. Genotype—phenotype correlation has been hampered by the variable sizes and breakpoints of the deletions. In this study, 14 novel patients with deletions in 3q11q23 were investigated and compared with 13 previously reported patients.

Methods Clinical data were collected from 14 novel patients that had been investigated by high resolution microarray techniques. Molecular investigation and updated clinical information of one cytogenetically previously reported patient were also included.

Results The molecular investigation identified deletions in the region 3q12.3q21.3 with different boundaries and variable sizes. The smallest studied deletion was 580 kb, located in 3q13.31. Genotype—phenotype comparison in 24 patients sharing this shortest region of overlapping deletion revealed several common major characteristics including significant developmental delay, muscular hypotonia, a high arched palate, and recognisable facial features including a short philtrum and protruding lips. Abnormal genitalia were found in the majority of males, several having micropenis. Finally, a postnatal growth pattern above the mean was apparent. The 580 kb deleted region includes five RefSeq genes and two of them are strong candidate genes for the developmental delay: DRD3 and ZBTB20.

Conclusion A newly recognised 3q13.31 microdeletion syndrome is delineated which is of diagnostic and prognostic value. Furthermore, two genes are suggested to be responsible for the main phenotype.

  • Developmental delay
  • microdeletion
  • overgrowth syndrome
  • genotype-phenotype
  • 3q

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

https://doi.org/10.1136/jmedgenet-2011-100534

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    Footnotes

    • Funding This study was supported by grants from the Sävstaholm Foundation, the Borgström Foundation, foundations at the Medical Faculty of Uppsala University, the Swedish Research Council, the Brazilian research foundations CNPq and FAPESP, and the Italian Ministry of Health.

    • Competing interests None.

    • Patient consent Obtained.

    • Ethics approval This study was approved by the ethics committee of Uppsala University.

    • Provenance and peer review Not commissioned; externally peer reviewed.