indicates that Notch2 influences the timing of puberty via interaction with the protein product of HERC2 (51) In this study, two siblings with apparently idiopathic CPP were found to harbor two heterozygous missense variations: p.Leu15Phe in NOTCH2 and p. Arg4081His in HERC2; the parents of these children each carried a single variant but did not have a history of precocious puberty (51). Here, NOTCH2 is linked to central precocious puberty.