title: Intragenic deletions of the IGF1 receptor gene in five individuals with psychiatric phenotypes and developmental delay.
abstract: Haploinsufficiency of the gene encoding the insulin-like growth factor 1 receptor (IGF1R), either caused by telomeric 15q26 deletions, or by heterozygous point mutations in IGF1R, segregate with short stature and various other phenotypes, including microcephaly and dysmorphic facial features. Psychomotor retardation and behavioral anomalies have been seen in some cases. Here we report small, intragenic deletions of IGF1R, identified by chromosome microarray analysis in two unrelated families affected primarily with neuropsychiatric phenotypes including developmental delay, intellectual disability and aggressive/autoaggressive behaviors. The deletions are in frame, and both wild-type and mutant mRNAs are expressed as measured by quantitative real-time PCR. While short stature is considered a phenotypic hallmark of IGF1R haploinsufficiency, the present report suggests that in frame exon deletions of IGF1R present predominantly with cognitive and neuropsychiatric phenotypes.
authors.affiliation: Department of Neurology, Charité University Medicine, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Witsch
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Szafranski
authors.forename: Chun-An
authors.initials: CA
authors.lastname: Chen
authors.forename: LaDonna
authors.initials: L
authors.lastname: Immken
authors.forename: Gayle
authors.initials: G
authors.lastname: Simpson Patel
authors.forename: Patricia
authors.initials: P
authors.lastname: Hixson
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Christian P
authors.initials: CP
authors.lastname: Schaaf
mesh_terms: D002648:Child; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics*; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D012333:RNA, Messenger; D017526:Receptor, IGF Type 1