Tommiska Johanna, Känsäkoski Johanna, Christiansen Peter, Jørgensen Niels, Lawaetz Jacob Gerner, Juul Anders, Raivio Taneli
Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland; Children's Hospital, Helsinki University Central Hospital (HUCH), Helsinki, Finland.
Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland; Children's Hospital, Helsinki University Central Hospital (HUCH), Helsinki, Finland.
Eur J Med Genet. 2014 Jul;57(7):345-8. doi: 10.1016/j.ejmg.2014.04.002. Epub 2014 Apr 13.
Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder characterized by incomplete/absent puberty caused by deficiency or defective action of gonadotropin-releasing hormone (GnRH). The phenotypic features of patients with CHH vary from genital hypoplasia and absent puberty to reversal of HH later in life. We examined the genetics and clinical features of CHH in Denmark. Forty-one male patients were screened for mutations in KAL1, FGFR1, FGF8, PROK2, PROKR2, GNRHR, TAC3, TACR3, and KISS1R. CHD7 was screened in two patients with hearing loss. In 12 patients, a molecular genetic cause for CHH was found. Four patients had mutations in KAL1 (C105VfsX13, C53X, ex5-8del, R257X), and five in FGFR1 (G97S, R209C, A512V, R646W, and c.1614C>T, (p.I538I), predicted to affect splicing). All 9 had severe HH (cryptorchidism and/or micropenis), and 2 had cleft lip/palate. One patient with a previously reported homozygous R262Q mutation in GNRHR displayed fascinating temporal variation in his phenotype. Two patients with hearing loss had CHD7 mutations (c.7832_7841del (p.K2611MfsX25) and c.2443-2A>C), confirming that CHH patients with CHARGE syndrome-associated features should be screened for mutations in CHD7.
先天性低促性腺激素性性腺功能减退（CHH）是一种罕见的疾病，其特征是由于促性腺激素释放激素（GnRH）缺乏或作用缺陷导致青春期不完全/缺失。CHH患者的表型特征从生殖器发育不全和青春期缺失到生命后期HH逆转不等。我们研究了丹麦CHH的遗传学和临床特征。对41名男性患者进行了KAL1、FGFR1、FGF8、PROK2、PROKR2、GNRHR、TAC3、TACR3和KISS1R基因突变筛查。对两名听力损失患者进行了CHD7筛查。在12名患者中，发现了CHH的分子遗传学原因。4名患者KAL1基因有突变（C105VfsX13、C53X、ex5 - 8del、R257X），5名患者FGFR1基因有突变（G97S、R209C、A512V、R646W和c.1614C>T，（p.I538I），预计影响剪接）。所有9名患者均有严重的HH（隐睾和/或小阴茎），2名患者有唇腭裂。一名先前报道的GNRHR基因纯合R262Q突变患者的表型呈现出迷人的时间变化。两名听力损失患者有CHD7基因突变（c.7832_7841del（p.K2611MfsX25）和c.2443 - 2A>C），证实对于具有CHARGE综合征相关特征的CHH患者应进行CHD7基因突变筛查。
