title: Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions.
abstract: Copy number variants (CNVs) and intragenic rearrangements of the NRXN1 (neurexin 1) gene are associated with a wide spectrum of developmental and neuropsychiatric disorders, including intellectual disability, speech delay, autism spectrum disorders (ASDs), hypotonia and schizophrenia. We performed a detailed clinical and molecular characterization of 24 patients who underwent clinical microarray analysis and had intragenic deletions of NRXN1. Seventeen of these deletions involved exons of NRXN1, whereas seven deleted intronic sequences only. The patients with exonic deletions manifested developmental delay/intellectual disability (93%), infantile hypotonia (59%) and ASDs (56%). Congenital malformations and dysmorphic features appeared infrequently and inconsistently among this population of patients with NRXN1 deletions. The more C-terminal deletions, including those affecting the β isoform of neurexin 1, manifested increased head size and a high frequency of seizure disorder (88%) when compared with N-terminal deletions of NRXN1.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Schaaf
authors.forename: Philip M
authors.initials: PM
authors.lastname: Boone
authors.forename: Srirangan
authors.initials: S
authors.lastname: Sampath
authors.forename: Charles
authors.initials: C
authors.lastname: Williams
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Bader
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Mueller
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Shchelochkov
authors.forename: Chester W
authors.initials: CW
authors.lastname: Brown
authors.forename: Heather P
authors.initials: HP
authors.lastname: Crawford
authors.forename: James A
authors.initials: JA
authors.lastname: Phalen
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Tartaglia
authors.forename: Patricia
authors.initials: P
authors.lastname: Evans
authors.forename: William M
authors.initials: WM
authors.lastname: Campbell
authors.forename: Anne Chun-Hui
authors.initials: AC
authors.lastname: Tsai
authors.forename: Lea
authors.initials: L
authors.lastname: Parsley
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Grayson
authors.forename: Angela
authors.initials: A
authors.lastname: Scheuerle
authors.forename: Carol D
authors.initials: CD
authors.lastname: Luzzi
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Thomas
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Eng
authors.forename: Sung-Hae L
authors.initials: SH
authors.lastname: Kang
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Sau W
authors.initials: SW
authors.lastname: Cheung
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000235:genetics; D056915:DNA Copy Number Variations; D005091:Exons / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D007438:Introns; D008297:Male; D046228:Microarray Analysis; D009123:Muscle Hypotonia / Q000151:congenital / Q000175:diagnosis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms