Human deficiency in IGF1R is involved in growth failure, microcephaly, mental retardation and deafness, and its overactivation is implicated in oncogenesis.
Patients with heterozygous mutations or deletions of IGF1R have a moderate pre- and postnatal growth failure, microcephaly and a history of feeding problems.
Heterozygous mutations in the IGF1 receptor (IGF1R) gene lead to partial resistance to IGF1 and contribute to intrauterine growth retardation (IUGR) with postnatal growth failure.
Our results show a novel missense mutation in the IGF1R gene (c.A1549T, p.Y487F) associated with prenatal and postnatal growth failure and microcephaly in the context of familial short stature.
Only the second compound heterozygous IGF1R mutations to be identified, the p.E121K/E234K variant is the cause of intrauterine growth retardation and the most severe postnatal growth failure described to date in a patient with IGF1R defects.
In addition, heterozygous mutations or gene deletions in the growth hormone-insulin-like growth factor (GH-IGF) axis such as the GH, GH-releasing hormone receptor, GH receptor, STAT5b, IGF-I, IGF-I receptor and the acid labile subunit have also been observed in children with growth failure and short stature.
Clinical and functional characteristics of a novel heterozygous mutation of the IGF1R gene and IGF1R haploinsufficiency due to terminal 15q26.2->qter deletion in patients with intrauterine growth retardation and postnatal catch-up growth failure.
Furthermore, while growth failure and mental retardation are primarily explained by loss of IGF1R, the occurrence of VSD might suggest the existence of a cardiac anomaly gene, other than the candidate cardiac anomaly gene NR2F2, in the deleted region.
MLPA and aCGH are useful tools to detect submicroscopic deletions of the IGF1R gene in patients born small for gestational age with persistent growth failure.
We postulated that mutations in the gene for the insulin-like growth factor I receptor (IGF-IR) might underlie some cases of prenatal and postnatal growth failure.
Individuals with a deletion of 15q26.1-->qter which contains the insulin-like growth factor-I (IGF-I) receptor gene exhibit phenotypical similarities to patients with Silver-Russell syndrome (SRS) who represent a group of short children affected by pre- and postnatal growth failure and several dysmorphic features.
The correlation between IGF1R gene dosage and growth retardation demonstrated here in our ring chromosome 15 patients suggests a possible role for heterozygous IGF1R gene mutations or deletions in other cases of unexplained growth failure.