Novel mutation of type-1 insulin-like growth factor receptor (IGF-1R) gene in a severe short stature pedigree identified by targeted next-generation sequencing.

Insulin-like growth factor receptor (IGF-1R) deficiency is a rare form of short stature, and is difficult to clinically diagnose. Targeted next-generation sequencing (NGS) allows for the rapid and inexpensive assessment of short stature. We identified mutations in the pedigree of a Chinese boy with severe short stature using targeted NGS; we then assessed the clinical characteristicsand evaluated the efficacy of growth hormone therapy. NGS analysis revealed a novel heterozygous missense mutation in exon3 (c.926C>T, p.S309L) of the type-I IGF-1R gene in the proband, which was inherited from the mother. The proband, mother and grandfather suffered from severe growth failure. After recombinant human growth hormone therapy, the patient's growth rate increased. The novel missensemutation in IGF-1R (c.926C > T, p.S309L) is associated with severe short stature in Chinese individuals. Targeted NGS may enable efficient diagnosis and genetic consultation of children with short stature.