Heterozygous Mutation within a Kinase-Conserved Motif of the Insulin-Like Growth Factor I Receptor Causes Intrauterine and Postnatal Growth Retardation

A prenatally disrupted airway epithelium orchestrates the fetal origin of asthma in mice

“…[80][81][82] Human and murine fetal lung development is crucially driven by IGF1/IGF1R signaling, which promotes vascular and epithelial differentiation as well as alveolarization. [83][84][85][86] Our results and those of others have shown a steadily increasing Igf1 and Igf1r expression throughout prenatal life in nonstressed murine offspring. 87 Importantly, in mice, IGF1 plays a predominately critical role during the late stages of fetal lung development, when it induces epithelial and vascular maturation, 87 thereby sustaining integrity of the epithelial barrier.…”

Increasing knowledge in IGF1R defects: lessons from 35 new patients

“…A few functional studies in either fibroblasts or cell lines have been reported, generally showing the inability of the mutated receptor to activate downstream pathways, especially phosphorylation of the receptor itself and/or AKT and rarely ERK 15–18. In 2009, Fang et al demonstrated IGF1R haploinsufficiency due to a mRNA decay phenomenon in a nonsense variant in exon 18 10.…”

Heterozygous nonsense mutations near the C‐terminal region of IGF1R in two patients with small‐for‐gestational‐age‐related short stature

“…IGF1R gene defect have been associated with intrauterine and postnatal growth retardation in over 20 families to date . It has been reported that there is phenotypic variability in the extent of growth retardation (−1·5 to −5·0 SDS; Table S1), but no genotype–phenotype correlations have been evident .…”

“…It has been reported that there is phenotypic variability in the extent of growth retardation (−1·5 to −5·0 SDS; Table S1), but no genotype–phenotype correlations have been evident . However, cases harbouring missense mutations in the α‐subunit of the receptor demonstrate a milder effect on stature than those with mutations in the β‐subunit, while cases with nonsense mutations (p.Q1250X, p.W1249X), frameshift mutations or microdeletions of IGF1R, which are considered to induce haploinsufficiency of the IGF1R protein, demonstrate a more severe or similar short stature phenotype as compared with cases with missense mutations (Table S1). Moreover, our cases with nonsense mutations that result in decreased expression of IGF1R protein demonstrated a degree of growth failure similar to those of known haploinsufficiency cases.…”

“…Heterozygous IGF1R anomalies that are associated with intrauterine and postnatal growth retardation have recently been observed in over 20 families . Results from previous studies have revealed that slight defects in IGF1R can affect human growth . These findings also suggested that IGF1R is crucial for growth, and emphasized the need for detailed evaluation of IGF1R function and of the clinical effects of IGF1R mutations.…”