Detection of Insulin-Like Growth Factor 1 Variants by Mass Spectrometry: Results from a Clinical Reference Laboratory

To the Editor: In 2011, Bystrom et al. developed a top-down liquid chromatography–high-resolution mass spectrometry (LC-HRMS)1 assay for insulin-like growth factor 1 (IGF-1) quantification (1). Using a similar method, Hines et al. subsequently reported a polymorphic IGF-1 variant, which they confirmed by DNA sequencing as A70T (2). Reports of other IGF-1 variants have involved isolated cases of patients in whom IGF-1 sequencing was performed because of a growth disorder. Known pathogenic IGF-1variants include V44M (3), R36Q (4), and R50W (5). We report here a DNA single nucleotide polymorphism (SNP) database-guided LC-HRMS approach to detect IGF-1 variants during routine clinical analysis. Intact wild-type (WT) IGF-1 and its variants were detected in 7 charged cysteine reduced …