Roles of Type 1 Insulin-Like Growth Factor (IGF) Receptor and IGF-II in Growth Regulation: Evidence From a Patient Carrying Both an 11p Paternal Duplication and 15q Deletion

Abstract

We report an original association of complex genetic defects in a patient carrying both an 11p paternal duplication, resulting in the double expression of insulin-like growth factor 2 (IGF2), as reported in Beckwith-Wiedemann syndrome, and a 15q terminal deletion, including the type 1 IGF receptor gene (IGF1R), resulting in haploinsufficiency for this gene. The patient was born with measurements appropriate for her gestational age but experienced growth retardation in early childhood, allowing a better comprehension of the IGF system in the pathophysiology of growth. It is possible that IGF-II plays a key role in fetal growth, independently of IGF1R signaling, and that its role is less important in post-natal growth, leaving IGF-I and growth hormone as the main actors.

Keywords: 11p duplication; Beckwith-Wiedemann syndrome; IGF-II; IGF1 receptor; fetal growth restriction; imprinting disease.

Figure 1

Schematic representation of 11p15 region gene expression.

Figure 2

Growth curve of the patient in centimeters and standard deviation score (SDS).

Figure 3

(A) Paired homologous chromosomes15 with Derivative chromosome 15 (left couple, on the right) and apparently normal 15 G-banded chromosomes 15 (middle couple) and (right couple). The two apparently normal chromosomes were then shown to carry a 15q terminal deletion (middle couple, on the right) and be a derivative chromosome 11 (right couple, on the right). (B) The SNP array profile shows a normal chromosome 21 (top), a heterozygous homogeneous 15q terminal deletion (middle, light purple area), and a mosaic gain on chromosome 11p (bottom, light purple area). (C) FISH [with a specific 11p subtelomeric probe (green), specific 15q22 probe (aqua blue), specific 15q subtelomeric probe (yellow), and specific subtelomeric 21q probe (red)] and schematic representation showing chromosomes 11, 15, and 21 in the three cell lines. First cell line with an unbalanced 15q;21p translocation. (D) Second cell line with a deleted 15q chromosome. The derivative chromosome 15 is missing a yellow signal. (E) Third cell line with an unbalanced 11p;15q translocation. The derivative chromosome 15 has a supernumerary green signal and no yellow signal.