Familial short stature and intrauterine growth retardation associated with a novel mutation in the IGF‐I receptor (IGF1R) gene

Abstract

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. The functional studies are in line with the inactivation of one copy of the IGF1R gene with variable expression within the same family.

Three novel IGF1R mutations in microcephalic patients with prenatal and postnatal growth impairment

“…Approximately 10–20% of children born small for gestational age (SGA) do not show spontaneous postnatal catch‐up growth, and the causes of pre‐ and postnatal growth deficit remain unclear in most cases. Since 2003, several IGF1R gene mutations have been described as a genetic cause of pre‐ and postnatal growth retardation due to IGF‐1 insensitivity in humans . These reports supported the important role of the IGF‐IGF1R signalling in growth control and the causal relationship between IGF1R gene mutations and SGA.…”

“…Moreover, the mother bearing the p.Tyr865Cys mutation showed stature within the normal range but presented microcephaly. Normal final height was reported in 4 affected cases, suggesting that there may be some recovery postnatal growth in some cases. However, all of these individuals had a history of low weight and/or length at birth and one patient also had microcephaly in adulthood .…”

“…Since the first description by Abuzzahab M et al . in 2003, several individuals from different families have been reported showing a great phenotypic and biochemical variability . It therefore seemed clinically relevant to define more appropriate selection criteria to look for this molecular diagnosis among children with weight and longitudinal growth deficiencies.…”

“…In SGA patients, the estimated frequency of IGF1R mutations previously reported ranged between 2 and 4% . However, subjects studied were selected according to different and strict criteria of growth restriction and biochemical parameters .…”

Alu-Mediated Recombination Defect in IGF1R: Haploinsufficiency in a Patient with Short Stature

“…Reports of around a dozen patients carrying IGF1R point mutations or small deletions or insertions have been published since 2003 of which some presented with minor comorbidities such as moderate mental retardation and developmental delay, impaired glucose homeostasis or mild facial dysmorphisms [5,6,7]. Moreover, large deletions of chromosome 15q26, including the IGF1R locus, have been described whose carriers - depending on size and position of the deletion - may show additional complications [8].…”