Clinical and Molecular Findings in 39 Patients with KBG Syndrome Caused by Deletion or Mutation of ANKRD11 - Université Claude Bernard Lyon 1 Accéder directement au contenu
Article Dans Une Revue American Journal of Medical Genetics Part A Année : 2016

Clinical and Molecular Findings in 39 Patients with KBG Syndrome Caused by Deletion or Mutation of ANKRD11

1 Service de génétique [Rouen]
2 GMGF - Génétique Médicale et Génomique Fonctionnelle
3 Department of Human Genetics
4 Département de génétique
5 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
6 Hôpital Jean Verdier [AP-HP]
7 GMFC - Génétique du cancer et des maladies neuropsychiatriques
8 CHU Rouen
9 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
10 CHU Pitié-Salpêtrière [AP-HP]
11 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
12 Service de Génétique Médicale [CHRU Nancy]
13 CHU Trousseau [APHP]
14 Physiopathologie et neuroprotection des atteintes du cerveau en développement
15 CHU de Bordeaux Pellegrin [Bordeaux]
16 Service de Cytogénétique
17 CINaM - Centre Interdisciplinaire de Nanoscience de Marseille
18 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
19 Service de génétique [Tours]
20 Service de Génétique
21 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
22 AGIM - AGeing and IMagery
23 Département de génétique [Robert Debré]
24 Centre de Maladies Rares
25 SESSTIM - U912 INSERM - Aix Marseille Univ - IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
26 IPC - Institut Paoli-Calmettes
27 BiosTIC - Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM]
28 Service de Génétique
Aude Tessier
  • Fonction : Auteur
Vincent Gatinois
Anne-Marie Guerrot
  • Fonction : Auteur
Francois Lecoquierre
  • Fonction : Auteur
Annick Toutain
Lionel van Maldergem
Arthur Sorlin
  • Fonction : Auteur
Chantal Missirian
  • Fonction : Auteur

Résumé

KBG syndrome, due to ANKRD11 alteration is characterized by developmental delay, short stature, dysmorphic facial features, and skeletal anomalies. We report a clinical and molecular study of 39 patients affected by KBG syndrome. Among them, 19 were diagnosed after the detection of a 16q24.3 deletion encompassing the ANKRD11 gene by array CGH. In the 20 remaining patients, the clinical suspicion was confirmed by the identification of an ANKRD11 mutation by direct sequencing. We present arguments to modulate the previously reported diagnostic criteria. Macrodontia should no longer be considered a mandatory feature. KBG syndrome is compatible with autonomous life in adulthood. Autism is less frequent than previously reported. We also describe new clinical findings with a potential impact on the follow-up of patients, such as precocious puberty and a case of malignancy. Most deletions remove the 5' end or the entire coding region but never extend toward 16q telomere suggesting that distal 16q deletion could be lethal. Although ANKRD11 appears to be a major gene associated with intellectual disability, KBG syndrome remains under-diagnosed. NGS-based approaches for sequencing will improve the detection of point mutations in this gene. Broad knowledge of the clinical phenotype is essential for a correct interpretation of the molecular results. (C) 2016 Wiley Periodicals, Inc.

Dates et versions

hal-01469066 , version 1 (16-02-2017)

Identifiants

Citer

Alice Goldenberg, Florence Riccardi, Aude Tessier, Rolph Pfundt, Tiffany Busa, et al.. Clinical and Molecular Findings in 39 Patients with KBG Syndrome Caused by Deletion or Mutation of ANKRD11. American Journal of Medical Genetics Part A, 2016, 170 (11), pp.2847-2859. ⟨10.1002/ajmg.a.37878⟩. ⟨hal-01469066⟩
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