reversible congenital hypogonadotropic hypogonadism in patients with chd7, fgfr1 or gnrhr mutations可逆的先天性hypogonadotropic chd7患者性腺机能减退,fgfr1或gnrhr突变.pdfVIP

Reversible Congenital Hypogonadotropic Hypogonadism in Patients with CHD7, FGFR1 or GNRHR Mutations 2 1,2 3 1,2 4,5 Eeva-Maria Laitinen , Johanna Tommiska , Timo Sane , Kirsi Vaaralahti , Jorma Toppari , Taneli Raivio1,2* 1 Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland, 2 Institute of Biomedicine/Physiology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland, 3 Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland, 4 Department of Physiology, University of Turku, Turku, Finland, 5 Department of Pediatrics, University of Turku, Turku, Finland Abstract Background: Congenital hypogonadotropic hypogonadism (HH) is a rare cause for delayed or absent puberty. These patients may recover from HH spontaneously in adulthood. To date, it is not possible to predict who will undergo HH reversal later in life. Herein we investigated whether Finnish patients with reversal of congenital hypogonadotropic hypogonadism (HH) have common phenotypic or genotypic features. Methods and Findings: Thirty-two male HH patients with anosmia/hyposmia (Kallmann Syndrome, KS; n = 26) or normal sense of smell (nHH; n = 6) were enrolled (age range, 18–61 yrs). The patients were clinically examined, and reversal of HH was assessed after treatment withdrawal. KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, WDR11, GNRHR, GNRH1, KISS1R, KISS1, TAC3, TACR3, and LHb were screened for mutations. Six HH patients (2 KS, 4 nHH) were verified to have reversal of HH. In the majority of cases, reversal occurred early in adulthood (median age, 23 yrs; range, 21–39 yrs). All had spontaneous testicular