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

Abstract

BackgroundDetection 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.ResultsTwo 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13039-014-0097-0) contains supplementary material, which is available to authorized users.

Screening for Subtelomeric Rearrangements in Thai Patients with Intellectual Disabilities Using FISH and Review of Literature on Subtelomeric FISH in 15,591 Cases with Intellectual Disabilities

“…For Patient 5, significance of 3p26.3 deletion was unclear. Deletion of this region was previously described in patients with ID and atypical autism [46]; however, it was also reported in four generations of a family that were apparently healthy [47]. …”

Clinical and Molecular Characterization of Two Patients with CNTN6 Copy Number Variations

“…Other malformations/ dysmorphisms were also found, including craniofacial and digital abnormalities and eye problems. In the 3 families reported by Kashevarova et al [2014], ID, psychomotor and growth retardation, microcephaly, and additional dysmorphic features were the common symptoms of CNTN6 CNVs. More recently, it has been suggested that microdeletions and point mutations of the CNTN6 gene may be associated with ASD and ID [Lin et al, 2016;Mercati et al, 2017].…”

“…Previously, Kashevarova et al [2014] reported 3 families with microdeletions/microduplications of the CNTN6 gene. Two families presented intragenic deletions in the 2nd intron (family F) and in the 20th intron (family N) of CNTN6 , while family K showed a duplication of the entire gene.…”

Chromosome r(3)(p25.3q29) in a Patient with Developmental Delay and Congenital Heart Defects: A Case Report and a Brief Literature Review

“…More studies of patients with r(3) and 3p deletions are required to figure out the causes for the hearing loss of our patient. Some other genes have also been studied to be associated with growth retardation, neurological deficits, and muscle disease, such as CHL1 , CNTN6, CNTN4, TRNT1, CRBN,SUMF1,ITPR1,GRM7,SRGAP3,BRPF1,MTMR14, and so on [Fernandez et al, 2004;Gibbs et al, 2010;Huang et al, 2012;Ellery et al, 2014;Kashevarova et al, 2014;Kotecha et al, 2014;Tassano et al, 2014;Fabbri et al, 2015;Liu et al, 2015;Papuc et al, 2015;You et al, 2015], which are all deleted in our patient. As a result, it is highly likely that several genes interact to contribute to the phenotypes associated with r(3) and 3p deletions.…”