title: Haploinsufficiency of XPO1 and USP34 by a de novo 230 kb deletion in 2p15, in a patient with mild intellectual disability and cranio-facial dysmorphisms.
abstract: 2p15p16.1-deletion syndrome was first described in 2007 based on the clinical presentation of two patients. The syndrome is characterized by intellectual disability, autism spectrum disorders, microcephaly, dysmorphic facial features and a variety of congenital organ defects. The precise genotype-phenotype correlation in 2p15-deletion syndrome is not understood. However, greater insight can be obtained by thorough clinical investigation of patients carrying deletions, especially those of small size. We report a 21-year-old male patient with features overlapping the clinical spectrum of the 2p15p16.1-deletion syndrome, such as intellectual disability, dysmorphic facial features, and congenital defects. He carried a 230 kb de novo deletion (chr2:61500346-61733075 bp, hg19), which affects the genes USP34, SNORA70B and XPO1. While there is a lack of functional data on SNORA70B, the involvement of USP34 and XPO1 in the regulation of fundamental developmental processes is well known. We suggest that haploinsufficiency of one or both of these genes is likely to be responsible for the disease in our patient.
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: uxmafa@ous-hf.no.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Fannemel
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: tuva.baroy@medisin.uio.no.
authors.forename: Tuva
authors.initials: T
authors.lastname: Barøy
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: asbjorn.holmgren@medisin.uio.no.
authors.forename: Asbjørn
authors.initials: A
authors.lastname: Holmgren
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: uxrdol@ous-hf.no.
authors.forename: Olaug K
authors.initials: OK
authors.lastname: Rødningen
authors.affiliation: Department for Adult Habilitation, Akershus University Hospital, Oslo, Norway. Electronic address: trine.haugsand@ahus.no.
authors.forename: Trine M
authors.initials: TM
authors.lastname: Haugsand
authors.affiliation: Department for Adult Habilitation, Akershus University Hospital, Oslo, Norway. Electronic address: borre.hansen@ahus.no.
authors.forename: Børre
authors.initials: B
authors.lastname: Hansen
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: eirik.frengen@medisin.uio.no.
authors.forename: Eirik
authors.initials: E
authors.lastname: Frengen
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: doriana.misceo@medisin.uio.no.
authors.forename: Doriana
authors.initials: D
authors.lastname: Misceo
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2; D055028:Comparative Genomic Hybridization; D019465:Craniofacial Abnormalities / Q000235:genetics*; D019066:Facies; D018740:Genetic Heterogeneity; D057895:Haploinsufficiency; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D028884:Karyopherins / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D010641:Phenotype; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D064570:Ubiquitin-Specific Proteases / Q000235:genetics*; D055815:Young Adult; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D064570:Ubiquitin-Specific Proteases; D000097606:Exportin 1 Protein; C584673:USP34 protein, human
keywords: 2p15p16.1 Deletion syndrome; Congenital anomalies; Dysmorphic features; Intellectual disability; USP34; XPO1 or CRM1