In addition, a large-scale whole exome sequencing had identified 4 individuals with POLR3B mutations in a large cohort of subjects with hypogonadotropic hypogonadism.[15] Kunii et al[16] had identified pathogenic mutations in 8 of the 60 adult leukoencephalopathy patients (one subject with POLR3A mutation) in Japan using a gene panel including 55 leukoencephalopathy-related genes. This evidence concerns the gene POLR3B and hypogonadotropic hypogonadism.