Simultaneous Detection of SMN1, SMN2, NAIP, H4F5, and GTF2H2 Copy Numbers and SMN1 Loss-of-Function Variants for SMA by MALDI-TOF Mass Spectrometry

Spinal muscular atrophy (SMA) is a common fatal genetic disorder with a high carrier rate. For the prevention program and treatment plan of this disease, a comprehensive assay is practically needed to gain multigenetic information, enabling effective molecular screening and accurate clinical classification. In this study, a novel single-tube matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry assay was developed to simultaneously analyze the copy numbers of survival motor neuron (SMN), neuronal apoptosis-inhibitory protein (NAIP), small EDRK-rich factor 1A (H4F5), and general transcription factor IIH subunit 2 (GTF2H2); identify six common loss-of-function variants in SMN1; and identify hybrid SMN.