Search for a gene responsible for Floating-Harbor syndrome on chromosome 12q15q21.1

Autor: Frédéric Huet, Alice Goldenberg, Armand Bottani, Sandy Lambert, Estelle Lopez, Laurence Duplomb, Bérénice Doray, Valérie Cormier-Daire, Patrick Callier, Anne Moncla, Bernard Aral, Laurence Faivre, Lucie Gueneau, Christel Thauvin-Robinet, Sylvie Odent, Damien Sanlaville, Didier Lacombe
Přispěvatelé: Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Laboratoire de cytogénétique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Génétique médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires de Genève (HUG), Laboratoire de Biologie de la reproduction CECOS - [CHU de Dijon], Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de Cytogénétique (HFME), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire de Génétique Chromosomique et Moléculaire [CHU Dijon], Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpitaux Universitaires de Genève ( HUG ), Service de Biologie Moléculaire, CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Sud, Service de Cytogénétique ( HFME ), Hôpital Femme Mère Enfant [CHU - HCL] ( HFME ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, Hospices Civils de Lyon (HCL)-Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), De Villemeur, Hervé
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Adult
Heart Septal Defects
Ventricular
Male
Candidate gene
Floating Harbor syndrome
[SDV.GEN] Life Sciences [q-bio]/Genetics
Haploinsufficiency
Biology
Bioinformatics
Short stature
Craniofacial Abnormalities
03 medical and health sciences
12q15q21.1 microdeletion
[SDV.BDD] Life Sciences [q-bio]/Development Biology
Genetics
medicine
Humans
Abnormalities
Multiple
Genetic Predisposition to Disease
[ SDV.BDD ] Life Sciences [q-bio]/Development Biology
Child
[SDV.BDD]Life Sciences [q-bio]/Development Biology
Genetics (clinical)
Growth Disorders
030304 developmental biology
Sequence Deletion
Phenocopy
0303 health sciences
Comparative Genomic Hybridization
[SDV.GEN]Life Sciences [q-bio]/Genetics
Chromosomes
Human
Pair 12
Genetic heterogeneity
030305 genetics & heredity
Chromosome
High-Throughput Nucleotide Sequencing
high-throughput sequencing
medicine.disease
3. Good health
Phenotype
Floating–Harbor syndrome
Child
Preschool
Mutation (genetic algorithm)
Female
medicine.symptom
[ SDV.GEN ] Life Sciences [q-bio]/Genetics
Zdroj: American Journal of Medical Genetics Part A
American Journal of Medical Genetics Part A, 2012, 158A (2), pp.333-9. ⟨10.1002/ajmg.a.34401⟩
American Journal of Medical Genetics Part A, Wiley, 2012, 158A (2), pp.333-9. 〈10.1002/ajmg.a.34401〉
American Journal of Medical Genetics Part A, Wiley, 2012, 158A (2), pp.333-9. ⟨10.1002/ajmg.a.34401⟩
ISSN: 1552-4825
1552-4833
Popis: International audience; Floating-Harbor syndrome (FHS) is characterized by characteristic facial dysmorphism, short stature with delayed bone age, and expressive language delay. To date, the gene(s) responsible for FHS is (are) unknown and the diagnosis is only made on the basis of the clinical phenotype. The majority of cases appeared to be sporadic but rare cases following autosomal dominant inheritance have been reported. We identified a 4.7 Mb de novo 12q15-q21.1 microdeletion in a patient with FHS and intellectual deficiency. Pangenomic 244K array-CGH performed in a series of 12 patients with FHS failed to identify overlapping deletions. We hypothesized that FHS is caused by haploinsufficiency of one of the 19 genes or predictions located in the deletion found in our index patient. Since none of them appeared to be good candidate gene by their function, a high-throughput sequencing approach of the region of interest was used in eight FHS patients. No pathogenic mutation was found in these patients. This approach failed to identify the gene responsible for FHS, and this can be explained by at least four reasons: (i) our index patient could be a phenocopy of FHS; (ii) the disease may be clinically heterogeneous (since the diagnosis relies exclusively on clinical features), (iii) these could be genetic heterogeneity of the disease, (iv) the patient could carry a mutation in a gene located elsewhere. Recent descriptions of patients with 12q15-q21.1 microdeletions argue in favor of the phenocopy hypothesis. © 2012 Wiley Periodicals, Inc.
Databáze: OpenAIRE
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