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16p13.11 microduplication in 45 new patients: refined clinical significance and genotype-phenotype correlations.
Allach El Khattabi, Laïla; Heide, Solveig; Caberg, Jean-Hubert; Andrieux, Joris; Doco Fenzy, Martine; Vincent-Delorme, Caroline; Callier, Patrick; Chantot-Bastaraud, Sandra; Afenjar, Alexandra; Boute-Benejean, Odile; Cordier, Marie Pierre; Faivre, Laurence; Francannet, Christine; Gerard, Marion; Goldenberg, Alice; Masurel-Paulet, Alice; Mosca-Boidron, Anne-Laure; Marle, Nathalie; Moncla, Anne; Le Meur, Nathalie; Mathieu-Dramard, Michèle; Plessis, Ghislaine; Lesca, Gaetan; Rossi, Massimiliano; Edery, Patrick; Delahaye-Duriez, Andrée; De Pontual, Loïc; Tabet, Anne Claude; Lebbar, Aziza; Suiro, Lesley; Ioos, Christine; Natiq, Abdelhafid; Chafai Elalaoui, Siham; Missirian, Chantal; Receveur, Aline; François-Fiquet, Caroline; Garnier, Pascal; Yardin, Catherine; Laroche, Cécile; Vago, Philippe; Sanlaville, Damien; Dupont, Jean Michel; Benzacken, Brigitte; Pipiras, Eva.
Afiliação
  • Allach El Khattabi L; Cytogenetics department, Cochin Hospital, Assistance Publique des Hôpitaux de Paris; Sorbonne Paris Cité, Paris Descartes University, Medical school, Paris, France.
  • Heide S; Department of Development, Reproduction and Cancer, Cochin Research Institute, INSERM U1016, CNRS UMR8104, Paris, France.
  • Caberg JH; Nuclear Lymphocyte Biology, NIAMS, National Institutes of Health, Bethesda, Maryland, United States.
  • Andrieux J; Cytogenetics department, Cochin Hospital, Assistance Publique des Hôpitaux de Paris; Sorbonne Paris Cité, Paris Descartes University, Medical school, Paris, France.
  • Doco Fenzy M; Genetics department, CHU de Liège - UniLab Lg, Liège, Belgium.
  • Vincent-Delorme C; Genetics department, Jeanne de Flandre Hospital, CHRU de Lille, Lille, France.
  • Callier P; Genetics department, CHU Reims, Medical school IFR53, EA3801, Reims, France.
  • Chantot-Bastaraud S; Genetics department, Guy Fontaine Medical center, CLAD Nord de France, Jeanne de Flandre Hospital, CHRU Lille, CH Arras, Arras, France.
  • Afenjar A; Genetics department, CHU de Dijon, Dijon, France.
  • Boute-Benejean O; Genetics and Embryology department, Armand-Trousseau Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France.
  • Cordier MP; Neuropediatrics department, Armand-Trousseau Hospital, Assistance Publique des Hôpitaux de Paris; Reference Center for cerebellar malformations, Paris, France.
  • Faivre L; Genetics department, Guy Fontaine Medical Center, CLAD Nord de France, Jeanne de Flandre Hospital, CHRU Lille, Lille, France.
  • Francannet C; Genetics department, GH Est, Hospices Civils de Lyon, Lyon, France.
  • Gerard M; Genetics department, CHU de Dijon, Dijon, France.
  • Goldenberg A; Medical Genetics department, Hôtel Dieu Hospital, Clermont-Ferrand, France.
  • Masurel-Paulet A; Genetics department, CHU Côte de Nacre, Caen, France.
  • Mosca-Boidron AL; Medical Genetics department, CHU Ch. Nicolle, Rouen, France.
  • Marle N; Genetics department, CHU de Dijon, Dijon, France.
  • Moncla A; Genetics department, CHU de Dijon, Dijon, France.
  • Le Meur N; Genetics department, CHU de Dijon, Dijon, France.
  • Mathieu-Dramard M; Medical Genetics department, CHU Timone enfants, Assistance Publique des Hôpitaux de Marseille, Marseille, France.
  • Plessis G; Department of Genetics, Reproductive biology and Histology, CHU de Rouen, Rouen, France.
  • Lesca G; Clinical Genetics department, CHU d'Amiens, Amiens, France.
  • Rossi M; Genetics department, CHU Côte de Nacre, Caen, France.
  • Edery P; Genetics department, GH Est, Hospices Civils de Lyon, Lyon, France.
  • Delahaye-Duriez A; GENDEV Team, CRNL, CNRS UMR 5292, INSERM U1028; Claude Bernard Lyon I University, Lyon, France.
  • De Pontual L; Genetics department, GH Est, Hospices Civils de Lyon, Lyon, France.
  • Tabet AC; GENDEV Team, CRNL, CNRS UMR 5292, INSERM U1028; Claude Bernard Lyon I University, Lyon, France.
  • Lebbar A; Genetics department, GH Est, Hospices Civils de Lyon, Lyon, France.
  • Suiro L; GENDEV Team, CRNL, CNRS UMR 5292, INSERM U1028; Claude Bernard Lyon I University, Lyon, France.
  • Ioos C; Department of Histology Embryology and Cytogenetics, Jean Verdier Hospital; Paris 13 University, Sorbonne Paris Cité, UFR SMBH Bobigny; PROTECT, INSERM, Paris Diderot University, Bondy, France.
  • Natiq A; Division of Brain Sciences, Faculty of Medicine, Imperial College, London, UK.
  • Chafai Elalaoui S; Pediatrics department, Jean Verdier Hospital, Assistance Publique des Hôpitaux de Paris, Paris 13 University, Bondy, France.
  • Missirian C; Genetics department, CHU Robert Debré, Assistance Publique des Hôpitaux de Paris, Paris, France.
  • Receveur A; Cytogenetics department, Cochin Hospital, Assistance Publique des Hôpitaux de Paris; Sorbonne Paris Cité, Paris Descartes University, Medical school, Paris, France.
  • François-Fiquet C; Neuropediatrics department, Hôpital Raymond Poincaré, Assistance Publique des Hôpitaux de Paris, Garches, France.
  • Garnier P; Neuropediatrics department, Hôpital Raymond Poincaré, Assistance Publique des Hôpitaux de Paris, Garches, France.
  • Yardin C; Medical Genetics department, Institut National d'Hygiène, Rabat, Morocco.
  • Laroche C; Medical Genetics department, Institut National d'Hygiène, Rabat, Morocco.
  • Vago P; Medical Genetics department, CHU Timone enfants, Assistance Publique des Hôpitaux de Marseille, Marseille, France.
  • Sanlaville D; Cytogenetics and Reproductive Biology department, CHU d'Amiens, Amiens, France.
  • Dupont JM; Plastic reconstructive and aesthetic surgery, Maison Blanche Hospital, Robert Debré Hospital, Reims, France.
  • Benzacken B; Pediatrics, CAMSP, Troyes, France.
  • Pipiras E; Department of Histology, Cytology, Cytogenetics, Cell Biology and Reproduction, Limoges University Hospital, Limoges, France.
J Med Genet ; 57(5): 301-307, 2020 05.
Article em En | MEDLINE | ID: mdl-30287593
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Deficiências do Desenvolvimento / MicroRNAs / Transtorno do Espectro Autista / Deficiência Intelectual / Proteínas Associadas aos Microtúbulos Tipo de estudo: Etiology_studies / Guideline / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Deficiências do Desenvolvimento / MicroRNAs / Transtorno do Espectro Autista / Deficiência Intelectual / Proteínas Associadas aos Microtúbulos Tipo de estudo: Etiology_studies / Guideline / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article