TY - JOUR
T1 - Genetics of congenital hypogonadotropic hypogonadism in Denmark
AU - Tommiska, Johanna
AU - Känsäkoski, Johanna
AU - Christiansen, Peter
AU - Jørgensen, Niels
AU - Lawaetz, Jacob Gerner
AU - Juul, Anders
AU - Raivio, Taneli
N1 - Copyright © 2014 Elsevier Masson SAS. All rights reserved.
PY - 2014/7
Y1 - 2014/7
N2 - 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.
AB - 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.
KW - DNA Helicases
KW - DNA-Binding Proteins
KW - Denmark
KW - Extracellular Matrix Proteins
KW - Genetic Diseases, Inborn
KW - Humans
KW - Hypogonadism
KW - Male
KW - Mutation
KW - Nerve Tissue Proteins
KW - Receptor, Fibroblast Growth Factor, Type 1
KW - Receptors, LHRH
U2 - 10.1016/j.ejmg.2014.04.002
DO - 10.1016/j.ejmg.2014.04.002
M3 - Journal article
C2 - 24732674
SN - 1769-7212
VL - 57
SP - 345
EP - 348
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 7
ER -