Single gene microdeletions and microduplication of 3p26.3 in three unrelated families: CNTN6 as a new candidate gene for intellectual disability

Anna A Kashevarova; Lyudmila P Nazarenko; Soren Schultz-Pedersen; Nikolay A Skryabin; Olga A Salyukova; Nataliya N Chechetkina; Ekaterina N Tolmacheva; Aleksey A Rudko; Pamela Magini; Claudio Graziano; Giovanni Romeo; Shelagh Joss; Zeynep Tümer; Igor N Lebedev

doi:10.1186/s13039-014-0097-0

Single gene microdeletions and microduplication of 3p26.3 in three unrelated families: CNTN6 as a new candidate gene for intellectual disability

Mol Cytogenet. 2014 Dec 31;7(1):97. doi: 10.1186/s13039-014-0097-0. eCollection 2014.

Authors

Affiliations

¹ Laboratory of Cytogenetics, Institute of Medical Genetics, 10 Nab. Ushaiki, 634050 Tomsk, Russia.
² Laboratory of Hereditary Pathology, Institute of Medical Genetics, Tomsk, Russia ; Department of Medical Genetics, Siberian State Medical University, Tomsk, Russia.
³ Private Pediatric Clinics "Bornelaegen Aarhus", Aarhus, Denmark.
⁴ Laboratory of Cytogenetics, Institute of Medical Genetics, 10 Nab. Ushaiki, 634050 Tomsk, Russia ; Laboratory of Human Ontogenetics, Tomsk State University, Tomsk, Russia.
⁵ Laboratory of Hereditary Pathology, Institute of Medical Genetics, Tomsk, Russia.
⁶ Genetic Clinic, Institute of Medical Genetics, Tomsk, Russia.
⁷ Unit of Medical Genetics, Department of Gynecology, Obstetrics and Pediatrics, University of Bologna, Bologna, Italy.
⁸ Department of Clinical Genetics, Level 2, Laboratory Medicine Building, Southern General Hospital, Glasgow, G51 4TF Scotland UK.
⁹ Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen Denmark.
¹⁰ Laboratory of Cytogenetics, Institute of Medical Genetics, 10 Nab. Ushaiki, 634050 Tomsk, Russia ; Department of Medical Genetics, Siberian State Medical University, Tomsk, Russia.

Abstract

Background: Detection of submicroscopic chromosomal alterations in patients with a idiopathic intellectual disability (ID) allows significant improvement in delineation of the regions of the genome that are associated with brain development and function. However, these chromosomal regions usually contain several protein-coding genes and regulatory elements, complicating the understanding of genotype-phenotype correlations. We report two siblings with ID and an unrelated patient with atypical autism who had 3p26.3 microdeletions and one intellectually disabled patient with a 3p26.3 microduplication encompassing only the CNTN6 gene.

Results: Two 295.1-kb microdeletions and one 766.1-kb microduplication of 3p26.3 involving a single gene, CNTN6, were identified with an Agilent 60K array. Another 271.9-kb microdeletion of 3p26.3 was detected using an Affymetrix CytoScan HD chromosome microarray platform. The CHL1 and CNTN4 genes, although adjacent to the CNTN6 gene, were not affected in either of these patients.

Conclusions: The protein encoded by CNTN6 is a member of the immunoglobulin superfamily and functions as a cell adhesion molecule that is involved in the formation of axon connections in the developing nervous system. Our results indicate that CNTN6 may be a candidate gene for ID.

Keywords: 3p26.3 microdeletion; 3p26.3 microduplication; CNTN6; Intellectual disability; Reciprocal microdeletions/microduplications.