Recently, IRs were shown to mediate complex duplication—inverted triplication—duplication (DUP-TRP/INV-DUP) rearrangements, leading to MECP2 duplication syndrome (MIM#300260), Duchenne Muscular Dystrophy (MIM#310200), VIPR2 triplication, CHRNA7 triplication, and Pelizaeus-Merzbacher disease (PMD, MIM#312080) [1,10–13]. The gene discussed is IARS1; the disease is Pelizeaus-Merzbacher spectrum disorder.