This repression imposed by MKRN3 on GNRH1 expression would be lost when the action of MKRN3 is impaired by loss-of-function mutations, as demonstrated by the in vivo ubiquitination assay performed on immortalized B lymphocytes derived from patients with CPP with MKRN3 defect (18). The gene discussed is GNRH1; the disease is central precocious puberty.