Mutation at Cleavage Site of Insulin-Like Growth Factor Receptor in a Short-Stature Child Born with Intrauterine Growth Retardation

Abstract

These findings strongly suggest that this mutation leads to failure of processing of the IGF-IR proreceptor to mature IGF-IR and causes short stature and IUGR.

Insulin-like growth factor signaling regulates zebrafish embryonic growth and development by promoting cell survival and cell cycle progression

“…5 Clinical studies have shown that human patients with lossof-function mutations in either IGF-1 or the IGF1R suffer severe intrauterine growth restriction and poor postnatal growth, as well as microcephaly, deafness and mental retardation. [6][7][8][9][10] Mouse genetic studies further established the causational importance of IGF1R signaling in fetal growth and development. IGF1R null mutant mice exhibited severe growth retardation at birth (45% of wild-type littermates) and died shortly after birth from respiratory failure.…”

Intragenic deletions of the IGF1 receptor gene in five individuals with psychiatric phenotypes and developmental delay

“…These were located in exons 2, 7, 11 and 16, respectively. [1][2][3][4][5] Short stature was present in all cases, mild motor and/or speech developmental delay in 4/9 cases and mild intellectual disabilitywith a Wechsler intelligence quotient of 60 -in one case of a patient with a missense mutation in exon 11. This missense mutation was detected in a girl whose mother, a carrier of the same mutation, did not show any neuropsychiatric abnormalities and had normal intelligence.…”

“…They were associated with various constellations of clinical findings, including growth deficit, microcephaly, developmental delay, mild facial dysmorphisms and skeletal deformations in affected individuals. [1][2][3][4][5][6][7][8][9][10][11] Usually intrauterine or postnatal growth deficits were moderate to severe in these patients. Notably, cognitive dysfunction of the reported individuals was either moderate, mild or absent.…”

“…Missense and nonsense mutations in IGF1R segregated with short stature, mild dysmorphic facial features, mostly mild developmental delay and mild psychiatric features in one reported case. [1][2][3][4][5] Although the variable phenotype of previously reported patients with 15q26.3 deletions may be attributable, at least in part, to genes other than IGF1R, it is notable that the smallest IGF1R deletion reported to date segregated predominantly with short stature and no or mild neuropsychiatric disorders. 10 In that family described by Veenma et al, seven family members carried a deletion of exons 11-21 of the IGF1R gene and what at the time of publication used to be a hypothetical protein-locus (LOC145814), and is now annotated as a RefSeq gene, PGPEP1L, encoding pyroglutamyl-peptidase-I-like.…”

“…Notably, cognitive dysfunction of the reported individuals was either moderate, mild or absent. [2][3][4] Significant psychiatric comorbidites beyond cognitive impairment have not been reported to date.…”