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CNTN6 copy number variations: Uncertain clinical significance in individuals with neurodevelopmental disorders.

Authors
  • Repnikova, Elena A1
  • Lyalin, Dmitry A2
  • McDonald, Kimberly3
  • Astbury, Caroline4
  • Hansen-Kiss, Emily5
  • Cooley, Linda D6
  • Pfau, Ruthann7
  • Herman, Gail E8
  • Pyatt, Robert E4
  • Hickey, Scott E9
  • 1 The Division of Clinical Genetics and Genomics Laboratories, Children's Mercy Hospital Kansas City, Kansas City, MO, 64108 USA; University Missouri-Kansas City School of Medicine, Kansas City, MO, 64108, USA. Electronic address: [email protected]
  • 2 The Division of Clinical Genetics and Genomics Laboratories, Children's Mercy Hospital Kansas City, Kansas City, MO, 64108 USA.
  • 3 Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
  • 4 Cytogenetics and Molecular Genetics Laboratory, Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
  • 5 Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, 43205, USA; Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, OH, 43205, USA.
  • 6 The Division of Clinical Genetics and Genomics Laboratories, Children's Mercy Hospital Kansas City, Kansas City, MO, 64108 USA; University Missouri-Kansas City School of Medicine, Kansas City, MO, 64108, USA.
  • 7 Cytogenetics and Molecular Genetics Laboratory, Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, 43205, USA; The Ohio State University College of Medicine, Columbus, OH, 43210, USA.
  • 8 Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, 43205, USA; Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, OH, 43205, USA; The Ohio State University College of Medicine, Columbus, OH, 43210, USA.
  • 9 Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, 43205, USA; The Ohio State University College of Medicine, Columbus, OH, 43210, USA. Electronic address: [email protected]
Type
Published Article
Journal
European journal of medical genetics
Publication Date
Jan 01, 2020
Volume
63
Issue
1
Pages
103636–103636
Identifiers
DOI: 10.1016/j.ejmg.2019.02.008
PMID: 30836150
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Copy number variations (CNVs) of the CNTN6 gene - a member of the contactin gene superfamily - have been previously proposed to have an association with neurodevelopmental and autism spectrum disorders. However, no functional evidence has been provided to date and phenotypically normal and mildly affected carriers complicate the interpretation of this aberration. In view of conflicting reports on the pathogenicity of CNVs involving CNTN6 and association with different phenotypes, we, independently, evaluated clinical features of nineteen patients with detected CNV of CNTN6 as part of their clinical microarray analysis at Children's Mercy and Nationwide Children's Hospitals for the period of 2008-2015. The clinical presentations of these patients were variable making it difficult to establish genotype-phenotype correlations. CNVs were inherited in six patients. For thirteen patients, inheritance pattern was not established due to unavailability of parental samples for testing. In three cases CNV was inherited from a healthy parent and in three cases from a parent with neurodevelopmental symptoms. Of the nineteen patients, four had a separate genetic abberation in addition to CNV of the CNTN6 that could independently explain their respective phenotypes. Separately, CNTN6 sequencing was performed on an autism spectrum disorder (ASD) research cohort of 94 children from 80 unrelated families. We found no difference in frequency of rare coding variants between the cohort of patients and controls. We conclude that CNVs involving CNTN6 alone seem to be most likely a neutral variant or a possible modifier rather than a disease-causing variant. Patients with CNVs encompassing CNTN6 could benefit from additional genetic testing since a clinical diagnosis due to a CNV of CNTN6 alone is still questionable. Copyright © 2019 Elsevier Masson SAS. All rights reserved.

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