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CNTN6 copy number variations: Uncertain clinical significance in individuals with neurodevelopmental disorders.
Repnikova, Elena A; Lyalin, Dmitry A; McDonald, Kimberly; Astbury, Caroline; Hansen-Kiss, Emily; Cooley, Linda D; Pfau, Ruthann; Herman, Gail E; Pyatt, Robert E; Hickey, Scott E.
Afiliação
  • Repnikova EA; 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: erepnikova@cmh.edu.
  • Lyalin DA; The Division of Clinical Genetics and Genomics Laboratories, Children's Mercy Hospital Kansas City, Kansas City, MO, 64108 USA.
  • McDonald K; Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
  • Astbury C; Cytogenetics and Molecular Genetics Laboratory, Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
  • Hansen-Kiss E; 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.
  • Cooley LD; 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.
  • Pfau R; 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.
  • Herman GE; 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.
  • Pyatt RE; Cytogenetics and Molecular Genetics Laboratory, Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
  • Hickey SE; Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, 43205, USA; The Ohio State University College of Medicine, Columbus, OH, 43210, USA. Electronic address: scott.hickey@nationwidechildrens.org.
Eur J Med Genet ; 63(1): 103636, 2020 Jan.
Article em En | MEDLINE | ID: mdl-30836150
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Contactinas / Transtornos do Neurodesenvolvimento Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Child / Female / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Contactinas / Transtornos do Neurodesenvolvimento Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Child / Female / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article