EPA-0644 - 3p26.3 - candidate loci of intellectual disability

Abstract

Introduction:To date 56 reciprocal microdeletion/microduplication syndromes have been described. Due to intensive application of microarray technologies new submicroscopic rearrangements are being published. The reciprocal rearrangements are particularly valuable, since they allow to determine the dosage-sensitive pathogenic genes.Objectives:To improve ID diagnostics.Aims:To identify novel candidate loci of ID.Methods:We performed the genome-wide analysis for 79 patients with idiopathic ID using CGH Microarray Kits 4×44K and 8×60K (Agilent Technologies, USA). Pathogenically significant cases were confirmed by qPCR.Results:We present two patients with microdeletion (369 kb) and microduplication (766 kb) at 3p26.3 containing the only gene - CNTN6. The microduplication was inherited from apparently healthy father. The child with microdeletion was an orphan. Recently, the microduplication in 3p26.3 (containing CNTN6) has been shown to be associated with autism spectrum disorders (ASDs). Contactin 6 is also suggested to play a neuroprotective role in ischemic injury and contribute to granule cell maturation and/or synaptic formation in the developing cerebellum.Considering the experiments with mice we found myotonic syndrome, late development of sit and walk ability in the anamnesis, current fine motor skills impairment and dysarthria in patient with dup3p26.3. His IQ is 47. Dysarthria was also observed in the patient with del3p26.3 (IQ 55).Conclusions:Obviously, CNTN6 can be a novel pathogenic gene associated with ASDs, ID, and motor functions impairment. This study was supported by EU Seventh Framework Program, CHERISH project no. 223692 and by Federal Program of Ministry of Education and Science of Russian Federation no. 8727.

Clinical evaluation of rare copy number variations identified by chromosomal microarray in a Hungarian neurodevelopmental disorder patient cohort

“…On the other hand, a high proportion of VUS were identi ed as well. Our diagnostic yield (40.4%) is quite high compared to the estimated 15-20% yield of CMA methods; but is comparable to several studies with similarly small patient groups (7,8). Comparing the detection rates of such CMA studies has always been confounded by differences in the applied array platforms and patient selection criteria.…”

7q35q36.3 Deletion and Concomitant 20q13.2q13.33 Duplication in a Newborn: Familiar Case

“…Unbalanced chromosomal rearrangements can be studied by Comparative Genomic Hybridization (array-CGH) that is able to identify at high resolution (5-10 Mb) the genetics causes of complex phenotypes usually only partially detectable (9.5%) by classical cytogenetics [2][3][4][5] . When the CGH array was not discovered these genomic alterations were called "idiopathic syndromes".…”