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Microtriplication of 11q24.1: a highly recognisable phenotype with short stature, distinctive facial features, keratoconus, overweight, and intellectual disability
  1. Claire Beneteau1,2,3,
  2. Emilie Landais4,
  3. Martine Doco-Fenzy4,
  4. Cyrille Gavazzi1,
  5. Christophe Philippe1,
  6. Mylène Béri-Dexheimer1,
  7. Céline Bonnet1,
  8. Jacqueline Vigneron3,
  9. Pierre Walrafen5,
  10. Jacques Motte6,
  11. Bruno Leheup2,
  12. Philippe Jonveaux1
  1. 1Laboratoire de Génétique, EA4368, Nancy-Université, CHUNancy, France
  2. 2Service de Médecine infantile 3et Génétique clinique, CHU de Nancy, France
  3. 3Service de Néonatologie-Génétique, Maternité Régionale Universitaire, Nancy, France
  4. 4Service de Génétique et EA3801, IFR53, UFR de médecine, CHRU de Reims, France
  5. 5Genomic Vision, Hôpital Cochin, Paris, France
  6. 6Unité de Neuropédiatrie, American Memorial Hospital, CHU de Reims, France
  1. Correspondence to Professor Philippe Jonveaux, Laboratoire de Génétique, EA 4368, Nancy Université, Centre Hospitalier Universitaire de Nancy, Hôpitaux de Brabois, rue de Morvan, 54511 Vandoeuvre les Nancy, France; p.jonveaux{at}chu-nancy.fr

Abstract

Background Partial tetrasomy is mainly described as a cytogenetically visible rearrangement due to a supernumerary chromosome (i(12p), i(18p), inv dup(15)). Except for chromosome 15q11q13, intrachromosomal triplications are rare and so far not associated with a recognisable phenotype.

Methods and results This report describes two unrelated patients with a de novo non-recurrent submicroscopic interstitial triplication 11q24.1 detected with array comparative genomic hybridisation and confirmed by fluorescence in situ hybridisation, molecular combing, and quantitative PCR. Microsatellite analysis suggested that a common mechanism of rearrangement might have been involved. These patients share remarkably similar clinical features including distinctive facial dysmorphisms, short stature with small extremities, keratoconus, overweight, and intellectual disability. The overlapping region of 1.8 Mb contains 11 RefSeq genes and three microRNA related genes. Interestingly, the overexpression of ASAM, a gene encoding an adipocyte specific adhesion molecule, may contribute to patients' obesity. Upregulation of BILD, known to mediate apoptosis in a caspase dependent manner, could deserve further investigation into the pathological mechanism of keratoconus.

Conclusion Isolated duplications of distal 11q region have been previously reported and associated with intellectual disability but without a consistent set of clinical features. These findings support the proposal that microtriplication 11q24.1 is a well recognisable clinical entity.

  • Microtriplication
  • 11q24.1
  • intellectual disability
  • obesity
  • keratoconus
  • array-CHG
  • genetics
  • genetic screening/counselling
  • genetic epidemiology
  • cytogenetics
  • diagnostics tests
  • epilepsy and seizures
  • molecular genetics
  • immunology (including allergy)
  • other endocrinology
  • drugs: endocrine system
  • molecular genetics
  • metabolic disorders
  • nutrition and metabolism
  • pituitary disorders
  • thyroid disease
  • diabetes
  • adrenal disorders
  • clinical genetics

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Footnotes

  • Funding Supported by French Ministry of Health (DHOS).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the University Hospital of Nancy.

  • Provenance and peer Not commissioned; externally peer reviewed

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