IGF1R Gene Alterations in Children Born Small for Gestitional Age (SGA)

Area of Science:

• Genetics
• Pediatrics
• Endocrinology

Background:

• Small for gestational age (SGA) children represent a diverse group with often unknown genetic etiologies.
• Previous research indicates that genetic alterations in the Insulin-like Growth Factor 1 Receptor (IGF1R) gene are implicated in some SGA cases.

Purpose of the Study:

• To investigate the presence of genetic alterations within the IGF1R gene in children born small for gestational age (SGA).
• To correlate identified genetic variants with growth patterns and serum IGF1 levels in SGA children.

Main Methods:

• Analysis of 64 short SGA children (mean SDS -3.25) and 36 SGA children who experienced catch-up growth.
• Screening of IGF1R coding exons using dHPLC and direct sequencing to detect small nucleotide variants.
• Assessment of IGF1R gene copy number alterations using Multiplex Ligation-dependent Probe Amplification (MLPA).

Main Results:

• Identified a heterozygous synonymous variant (c.3453C > T) in one short SGA patient.
• Discovered a novel heterozygous 3 bp in-frame deletion (c.3234_3236delCAT) in another short SGA patient, leading to an amino acid deletion (p.Ile1078del).
• The patient with the deletion presented with significantly low serum IGF1 levels (-1.57 SD), contrasting with typical findings.

Conclusions:

• IGF1R gene alterations were found in 2 out of 64 short SGA children, without dysmorphic features or developmental delay.
• One patient showed significantly decreased IGF1 concentrations, a notable observation in SGA genetics.
• Favorable growth response to growth hormone (GH) treatment was observed in one patient; the other experienced catch-up growth after discontinuing treatment.