Article Dans Une Revue Journal of Medical Genetics Année : 2018

16p13.11 microduplication in 45 new patients: refined clinical significance and genotype–phenotype correlations

1 Hôpital Cochin [AP-HP]
2 UPD5 - Université Paris Descartes - Paris 5
3 USPC - Université Sorbonne Paris Cité
4 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine
5 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
6 IC UM3 (UMR 8104 / U1016) - Institut Cochin
7 DRC - [Institut Cochin] Département Développement, Reproduction et Cancer
8 CHU-Liège - Centre Hospitalier Universitaire de Liège
9 Laboratoire de Génétique Médicale [Hôpital Jeanne de Flandre]
10 Hôpital Jeanne de Flandre [Lille]
11 CHU Reims - Hôpital universitaire Robert Debré [Reims]
12 IFR53
13 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
14 CHU Trousseau [APHP]
15 CHU Pitié-Salpêtrière [AP-HP]
16 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
17 HCL - Hospices Civils de Lyon
18 GAD - Génétique des Anomalies du Développement
19 Service Génétique Médicale [CHU Clermont-Ferrand]
20 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
21 Hôpital Côte de Nacre [CHU Caen]
22 Service de génétique [Rouen]
23 Laboratoire de cytogénétique (CHU de Dijon)
24 Département de génétique médicale [Hôpital de la Timone - APHM]
25 CHU Amiens-Picardie
26 Service de Génétique [CHU Caen]
27 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
28 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
29 Hôpital Jean Verdier [AP-HP]
30 Inserm U393 - Handicaps génétiques de l'enfant
31 Département de génétique
32 AP-HP Hôpital universitaire Robert-Debré [Paris]
33 Hôpital Raymond Poincaré [AP-HP]
34 Département de Génétique Médicale [INH Rabat]
35 Service d'histologie, embryologie et cytogénétique [Béclère]
36 Hôpital Maison Blanche
37 Hôpital Robert Debré
38 ERMA - Equipe de Recherche Médicale Appliquée
39 XLIM-BIO-INGENIERIE - BIO-INGENIERIE
40 Service de Pédiatrie médicale [CHU Limoges]
41 IMoST - Imagerie Moléculaire et Stratégies Théranostiques
Sandra Chantot-Bastaraud
Alexandra Afenjar
  • Fonction : Auteur
  • PersonId : 902592
Alice Goldenberg
Michèle Mathieu-Dramard
Christine Ioos
  • Fonction : Auteur
  • PersonId : 902591
Pascal Garnier
  • Fonction : Auteur

Résumé

Background: The clinical significance of 16p13.11 duplications remains controversial while frequently detected in patients with developmental delay (DD), intellectual deficiency (ID) or autism spectrum disorder (ASD). Previously reported patients were not or poorly characterised. The absence of consensual recommendations leads to interpretation discrepancy and makes genetic counselling challenging. This study aims to decipher the genotype-phenotype correlations to improve genetic counselling and patients' medical care. Methods: We retrospectively analysed data from 16 013 patients referred to 12 genetic centers for DD, ID or ASD, and who had a chromosomal microarray analysis. The referring geneticists of patients for whom a 16p13.11 duplication was detected were asked to complete a questionnaire for detailed clinical and genetic data for the patients and their parents. Results: Clinical features are mainly speech delay and learning disabilities followed by ASD. A significant risk of cardiovascular disease was noted. About 90% of the patients inherited the duplication from a parent. At least one out of four parents carrying the duplication displayed a similar phenotype to the propositus. Genotype-phenotype correlations show no impact of the size of the duplicated segment on the severity of the phenotype. However, NDE1 and miR-484 seem to have an essential role in the neurocognitive phenotype. Conclusion: Our study shows that 16p13.11 microduplications are likely pathogenic when detected in the context of DD/ID/ASD and supports an essential role of NDE1 and miR-484 in the neurocognitive phenotype. Moreover, it suggests the need for cardiac evaluation and follow-up and a large study to evaluate the aortic disease risk.

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Dates et versions

hal-01926555 , version 1 (06-07-2023)

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Laïla Allach El Khattabi, Solveig Heide, Jean-Hubert Caberg, Joris Andrieux, Martine Doco Fenzy, et al.. 16p13.11 microduplication in 45 new patients: refined clinical significance and genotype–phenotype correlations. Journal of Medical Genetics, 2018, ⟨10.1136/jmedgenet-2018-105389⟩. ⟨hal-01926555⟩
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