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.

Insulin‐Like Growth Factor and Insulin‐Like Growth Factor Receptor Expression in Human Idiopathic Autism Fusiform Gyrus Tissue

“…There were no differences in either the IGF-1R mRNA or protein levels. Both increased and decreased expression of the gene coding for IGF-1R (IGF1R) may play a role in the etiology of neurological disorders, as previous studies have described [Cannarella et al, 2017;Witsch et al, 2013]. We are the first to report on the levels of IGF-1R in human idiopathic autism.…”

IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

“…Patients with this syndrome experience less growth after birth and this becomes more severe with age, leading to smaller brain size, smaller heart, less muscle development, among other deficits (Puche and Castilla-Cortázar, 2012 ). Although short stature is a common feature of the individuals bearing IGF-I and/or IGF-IR mutations, a recent study has described intragenic deletions of the IGF-IR associated to a developmental delay and intellectual disability of five people that do not have a significant short stature (Witsch et al, 2013 ).…”

Insulin and IGF receptor signalling in neural-stem-cell homeostasis

“…73 Of particular interest to this Review are the reports of microcephaly, neuropsychiatric disorders and intellectual deficits resulting from mutations in IGF1 or IGF1R in humans. 73–75 …”