Familial Short Stature Caused by Haploinsufficiency of The Insulin-like Growth Factor 1 Receptor Due to Nonsense-Mediated mRNA Decay

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

“…Phenotypic findings in carriers of the G1125A mutation are in line with earlier reports arguing for the pathogenic effect of heterozygous IGF1R mutations (3)(4)(5)(6)(7)(8). So far, affected individuals described here and earlier mainly presented with intrauterine and postnatal growth retardation and microcephaly.…”

“…However, IGF-I deficiency and IGF-I resistance have been reported in patients with intrauterine and postnatal growth retardation, suggesting disturbances in IGF-I signaling as a possible cause (1)(2)(3)(4)(5)(6)(7)(8).…”

“…Few human IGF1R mutations were identified in heterozygous carriers presenting with mild to severe intrauterine and postnatal growth retardation and variable additional findings. Mutations described to date led to IGF1R haploinsufficiency (4,5), disturbed processing of the proreceptor (6), impaired ligand binding (3), and reduced autophosphorylation (7,8).…”