Disruption of EXOC6B in a patient with developmental delay, epilepsy, and a de novo balanced t(2;8) translocation

• Published in: European journal of human genetics : EJHG Vol. 21; no. 10; pp. 1177 - 1180
• Main Authors: Frühmesser, Anne, Blake, Jonathon, Haberlandt, Edda, Baying, Bianka, Raeder, Benjamin, Runz, Heiko, Spreiz, Ana, Fauth, Christine, Benes, Vladimir, Utermann, Gerd, Zschocke, Johannes, Kotzot, Dieter
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-10-2013
• Subjects: Abnormalities, Multiple - genetics; Abnormalities, Multiple - metabolism; Age; Alu elements; Autism; Behavior; Breakpoints; Chromosome 19; Chromosome 8; Chromosome aberrations; Chromosome Breakpoints; Chromosome rearrangements; Chromosomes; Chromosomes, Human, Pair 2 - genetics; Chromosomes, Human, Pair 8 - genetics; Developmental Disabilities - genetics; Developmental Disabilities - metabolism; Epilepsy; Epilepsy - genetics; Epilepsy - metabolism; Female; Genetic counseling; Genetics; Genomes; Genotype & phenotype; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Homology; Humans; Intellectual development; Intellectual disabilities; Laboratories; Lymphocytes; Lymphocytes - metabolism; Molecular biology; Mouth Mucosa - metabolism; Mutation; Patients; Phenotypes; Short Report; Syndrome; Translocation, Genetic; Young Adult; Austria; Germany
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/ejhg.2013.18

Most balanced chromosomal aberrations are not associated with a clinical phenotype, however, in some patients they may disrupt gene structure. With the development of various next-generation sequencing techniques, fast and specific analyses of the breakpoint regions of chromosomal rearrangements are possible. Here, we report on a 19-year-old woman with a de novo balanced translocation t(2;8)(p13.2;q22.1) and a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features. By next-generation sequencing, we defined the breakpoints and found disruption of the exocyst complex component 6B (EXOC6B) gene in intron 1 on chromosome 2p13.2 involving two Alu elements with a homology of 81%. No gene was found at the respective breakpoint on chromosome 8. Expression analysis of the EXOC6B in blood lymphocytes and buccal smear revealed reduced expression in the patient in comparison with the control. Our findings in combination with one recently published case and one other patient listed in DECIPHER v5.1 indicate EXOC6B as a gene relevant for intellectual development and electrophysiological stability.