1. Refinement of Genotype-Phenotype Correlation in 18 Patients Carrying a 1q24q25 Deletion
- Author
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Caroline Schluth-Bolard, Claudia A. L. Ruivenkamp, Brigitte Benzacken, Zeynep Tümer, Joris Andrieux, Nicole Bain, Kerry Fagan, Nicolas Chatron, Marianne Till, Damien Sanlaville, Clarisse Baumann, Odile Boute, P. Edery, Laura Bernardini, Céline Bonnet, Anna Hackett, Massimiliano Rossi, Bruno Leheup, Julie Désir, Arie van Haeringen, Séverine Drunat, Yves Alembik, Véronique Haddad, Marion Gérard, Pia Castelluccio, Anne Dieux, Helen Stewart, Azzedine Aboura, Elisabeth Flori, Laura Roos, Joanna McParland, Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon], Hospices Civils de Lyon (HCL), Unité de Cytogénétique [CHU Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Service de Génétique clinique, Unité de Génétique Clinique [CHU Debré], Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de génétique [Hôpial Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Cytogénétique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Génétique Clinique [Hautepierre Strasbourg], Hôpital de Hautepierre [Strasbourg], Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Mendel Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Ospedale Cardarelli, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University of Newcastle [Australia] (UoN), Department of Clinical Genetics, Leiden University Medical Centre, Clinical Cytogeneticist Laboratory for Diagnostic Genome Analysis [Leiden University Medical Center], Leiden University Medical Center (LUMC), Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Cytogénétiqué, Hôpital Jean-Verdier, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Newcastle [Callaghan, Australia] (UoN), Universiteit Leiden-Universiteit Leiden, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Adult ,Male ,Microcephaly ,Pathology ,medicine.medical_specialty ,Microarray ,Adolescent ,[SDV]Life Sciences [q-bio] ,growth retardation ,Biology ,Single transverse palmar crease ,Genetics ,medicine ,Humans ,1q24q25 deletion ,Sex organ ,Abnormalities, Multiple ,10. No inequality ,Child ,Genetics (clinical) ,Genetic Association Studies ,In Situ Hybridization, Fluorescence ,Aged ,Comparative Genomic Hybridization ,Brachydactyly ,Infant, Newborn ,brachydactyly ,Chromosome ,Infant ,Middle Aged ,DNM3 ,medicine.disease ,Phenotype ,Chromosomes, Human, Pair 1 ,intellectual disability ,Child, Preschool ,Female ,medicine.symptom ,Chromosome Deletion - Abstract
International audience; Interstitial deletion 1q24q25 is a rare rearrangement associated with intellectual disability, growth retardation, abnormal extremities and facial dysmorphism. In this study, we describe the largest series reported to date, including 18 patients (4M/14F) aged from 2 days to 67 years and comprising two familial cases. The patients presented with a characteristic phenotype including mild to moderate intellectual disability (100%), intrauterine (92%) and postnatal (94%) growth retardation, microcephaly (77%), short hands and feet (83%), brachydactyly (70%), fifth finger clinodactyly (78%) and facial dysmorphism with a bulbous nose (72%), abnormal ears (67%) and micrognathia (56%). Other findings were abnormal palate (50%), single transverse palmar crease (53%), renal (38%), cardiac (38%), and genital (23%) malformations. The deletions were characterized by chromosome microarray. They were of different sizes (490 kb to 20.95 Mb) localized within chromosome bands 1q23.3-q31.2 (chr1:160797550-192912120, hg19). The 490 kb deletion is the smallest deletion reported to date associated with this phenotype. We delineated three regions that may contribute to the phenotype: a proximal one (chr1:164,501,003-167,022,133), associated with cardiac and renal anomalies, a distal one (chr1:178,514,910-181,269,712) and an intermediate 490 kb region (chr1:171970575-172460683, hg19), deleted in the most of the patients, and containing DNM3, MIR3120 and MIR214 that may play an important role in the phenotype. However, this genetic region seems complex with multiple regions giving rise to the same phenotype.
- Published
- 2015