title: Mosaic deletion of EXOC6B: further evidence for an important role of the exocyst complex in the pathogenesis of intellectual disability.
abstract: 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 diaphysis 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 contractures. 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 behavior. This is the first report of a de novo deletion affecting only EXOC6B in an individual with developmental delay. In conclusion, 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 intellectual disability.
authors.affiliation: Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Evers
authors.forename: Bianca
authors.initials: B
authors.lastname: Maas
authors.forename: Karin A
authors.initials: KA
authors.lastname: Koch
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.forename: Johannes W G
authors.initials: JW
authors.lastname: Janssen
authors.forename: Christian
authors.initials: C
authors.lastname: Sutter
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parker
authors.forename: Katrin
authors.initials: K
authors.lastname: Hinderhofer
authors.forename: Ute
authors.initials: U
authors.lastname: Moog
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D057895:Haploinsufficiency / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D014421:Turkey
chemical_list: C489222:EXOC6B protein, human; D019204:GTP-Binding Proteins
keywords: 2p13.2 deletion; EXOC6B; developmental delay; exocyst complex; intellectual disability