Traduction : G.M.
J Autism Dev Disord. 2016 Nov 16.
The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications
Gillentine MA1,2, Berry LN3,4, Goin-Kochel RP3,4, Ali MA1,2, Ge J1, Guffey D5, Rosenfeld JA1, Hannig V6, Bader P7, Proud M4,8, Shinawi M9, Graham BH1, Lin A10, Lalani SR1, Reynolds J11, Chen M12, Greb T13, Minard CG5, Stankiewicz P1, Beaudet AL1, Schaaf CP14,15.
Author information
- 1Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
- 2Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Moursund Street, Ste. 1325, Houston, TX, USA.
- 3Autism Center, Texas Children's Hospital, Houston, TX, USA.
- 4Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
- 5Dan L. Duncan Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
- 6Department of Pediatrics, Vanderbilt University Medical Center, Nashville, USA.
- 7Northeast Indiana Genetics, Fort Wayne, IN, USA.
- 8Department of Neurology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
- 9Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
- 10Medical Genetics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, USA.
- 11Medical Genetics, Shodair Children's Hospital, Helena, MT, USA.
- 12Department of Pediatrics-Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
- 13Department of Child Health, Division of Genetics and Metabolism, Phoenix Children's Hospital, University of Arizona College of Medicine, Phoenix, AZ, USA.
- 14Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. schaaf@bcm.edu.
- 15Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Moursund Street, Ste. 1325, Houston, TX, USA. schaaf@bcm.edu
Abstract
Le chromosome 15q11q13 est parmi les régions les moins stables dans le génome en raison de son architecture génomique très complexe. Les éléments de répétition de copie faible sur 15q13.3 facilitent les variations du nombre de copie récurrentes (VNC), avec des délétions établies comme pathogènes et CHRNA7 est impliqué comme gène candidat. Cependant, la pathogénicité des doublons de CHRNA7 n'est pas claire, car ils sont trouvés chez les probands touchés ainsi que chez les parents déclarés en bonne santé et les individus témoins non affectés. Nous avons évalué 18 enfants présentant des micro doublements impliquant CHRNA7, identifiés par une analyse avec puces à ADN clinique (CMA pour chromosome
microarray analysis). Le phénotypage complet a révélé une prévalence élevée de retard de développement / déficience intellectuelle, trouble du spectre de l'autisme et trouble déficitaire de l'attention / hyperactivité. Comme les duplications de CHRNA7 sont les VNC les plus courantes identifiées par les CMA cliniques, cette étude fournit des conseils prévisionnels pour les personnes concernées par les soins des personnes touchées.
Chromosome 15q11q13 is among the least stable regions in the genome due to its highly complex genomic architecture. Low copy repeat elements at 15q13.3 facilitate recurrent copy number variants (CNVs), with deletions established as pathogenic and CHRNA7 implicated as a candidate gene. However, the pathogenicity of duplications of CHRNA7 is unclear, as they are found in affected probands as well as in reportedly healthy parents and unaffected control individuals. We evaluated 18 children with microduplications involving CHRNA7, identified by clinical chromosome microarray analysis (CMA). Comprehensive phenotyping revealed high prevalence of developmental delay/intellectual disability, autism spectrum disorder, and attention deficit/hyperactivity disorder. As CHRNA7 duplications are the most common CNVs identified by clinical CMA, this study provides anticipatory guidance for those involved with care of affected individuals.
Chromosome 15q11q13 is among the least stable regions in the genome due to its highly complex genomic architecture. Low copy repeat elements at 15q13.3 facilitate recurrent copy number variants (CNVs), with deletions established as pathogenic and CHRNA7 implicated as a candidate gene. However, the pathogenicity of duplications of CHRNA7 is unclear, as they are found in affected probands as well as in reportedly healthy parents and unaffected control individuals. We evaluated 18 children with microduplications involving CHRNA7, identified by clinical chromosome microarray analysis (CMA). Comprehensive phenotyping revealed high prevalence of developmental delay/intellectual disability, autism spectrum disorder, and attention deficit/hyperactivity disorder. As CHRNA7 duplications are the most common CNVs identified by clinical CMA, this study provides anticipatory guidance for those involved with care of affected individuals.
- PMID: 27853923
- DOI: 10.1007/s10803-016-2961-8
