RESEARCH ARTICLE Mosaic Deletion of E XOC6B: Further Evidence for An Important Role of the Exocyst Complex in the Pathogenesis of Intellectual Disability Christina Evers, 1 * Bianca Maas, 1 Karin A. Koch, 2 Anna Jauch, 1 Johannes W.G. Janssen, 1 Christian Sutter, 1 Michael J. Parker, 3 Katrin Hinderhofer, 1 and Ute Moog 1 1 Institute of Human Genetics, Heidelberg University, Heidelberg, Germany 2 Department of Pediatrics, University Children’s Hospital, Heidelberg, Germany 3 Sheffield Clinical Genetics Services, Sheffield Children’s Hospital, Sheffield, UK Manuscript Received: 30 December 2013; Manuscript Accepted: 7 August 2014 We describe a boy with developmental delay, speech delay, and minor dysmorphic features with a heterozygous de novo 460 kb deletion at 2p13.2 involving only parts of EXOC6B present in about 50% of lymphocytes. This widely expressed gene encodes the exocyst component 6B, which is part of a multiprotein complex required for targeted exocytosis. Little is known about the effect of EXOC6B haploinsufficiency. In 2008, a patient with a complex syndromic phenotype, including left renal agenesis, neutropenia, recurrent pulmonary infections, long bone diaphy- sis broadening, growth retardation, and developmental delay (DD) was found to carry a de novo translocation t(2;7) involving TSN3 and EXOC6B. Further characterization of the translocation indicated that disruption of TSN3 may be responsible for the skeletal phenotype. Recently, a heterozygous deletion of EXOC6B along with a deletion of the CYP26B1 gene has been reported in a boy with intellectual disability, speech delay, hyperactivity, facial asymmetry, a dysplastic ear, brachycephaly, and mild joint con- tractures. Additionally, disruption of EXOC6B by a de novo balanced translocation t(2;8) has been described in a patient with developmental delay, epilepsy, autistic and aggressive be- havior. This is the first report of a de novo deletion affecting only EXOC6B in an individual with developmental delay. In conclu- sion, based on our findings and recent data from the literature, there is evidence that EXOC6B and the exocyst complex might play an important role in the molecular pathogenesis of intellec- tual disability. Ó 2014 Wiley Periodicals, Inc. Key words: 2p13.2 deletion; EXOC6B; exocyst complex; intellectual disability; developmental delay INTRODUCTION Ten to fourteen percent of intellectual disability (ID) is caused by submicroscopic chromosome deletions or duplications [Hochsten- bach et al., 2011]. Based on recent studies using next generation sequencing (NGS) techniques there is evidence that dominant de novo mutations account for a considerable proportion of ID [de Ligt et al., 2012; Rauch et al., 2012]. High-resolution microarrays can contribute to the detection of both microdeletions and single gene aberrations, and multiple autosomal dominant gene defects have been identified by this method. We describe a small deletion affecting only part of the EXOC6B gene (also known as SEC15B and SEC15L2) in a boy with developmental delay (DD). Although little is known about the function of EXOC6B in humans, our findings and recent data from the literature indicate that EXOC6B is a strong candidate gene for autosomal dominant ID. CLINICAL REPORT The boy was the first child of nonconsanguineous healthy parents from Turkey. He was delivered in breech presentation by cesarean after 40 weeks of gestation with normal birth parameters (weight 3180 g, 10th–25th centile; length 51 cm, 25th centile; OFC 33.5 cm, How to Cite this Article: Evers C, Maas B, Koch KA, Jauch A, Janssen JWG, Sutter C, Parker MJ, Hinderhofer K, Moog U. 2014. Mosaic deletion of EXOC6B: Further evidence for an important role of the exocyst complex in the pathogenesis of intellectual disability. Am J Med Genet Part A 164A:3088–3094. Christina Evers and Bianca Maas have contributed equally to this work.  Correspondence to: Christina Evers, and Bianca Maas, Institute of Human Genetics Heidelberg University, Im Neuenheimer Feld 366, Heidelberg, 69120, Germany. E-mail: christina.evers@med.uni-heidelberg.de (C.E.) Article first published online in Wiley Online Library (wileyonlinelibrary.com): 24 September 2014 DOI 10.1002/ajmg.a.36770 Ó 2014 Wiley Periodicals, Inc. 3088