Isolated cryptorchidism: No evidence for involvement of genes underlying isolated hypogonadotropic hypogonadism

Mutations in FGFR1, GNRHR, PROK2, PROKR2, TAC3, or TACR3 underlie isolated hypogonadotropic hypogonadism (IHH) with clinically variable phenotypes, and, by causing incomplete intrauterine activation of the hypothalamic–pituitary–gonadal axis, may lead to cryptorchidism. To investigate the role of defects in these genes in the etiology of isolated cryptorchidism, we screened coding exons and exon–intron boundaries of these genes in 54 boys or men from 46 families with a history of cryptorchidism. Control subjects (200) included 120 males. None of the patients carried mutation(s) in FGFR1, PROK2, PROKR2, TAC3 or TACR3. Two of the 46 index subjects with unilateral cryptorchidism were heterozygous carriers of a single GNRHR mutation (Q106R or R262Q), also present in male controls with a similar frequency (3/120; p = 0.62). No homozygous or compound heterozygous GNRHR mutations were found. In conclusion, cryptorchidism is not commonly caused by defects in genes involved in IHH.

► We investigated the defects in FGFR1, GNRHR, PROK2, PROKR2, TAC3, and TACR3 in 54 subjects with isolated cryptorchidism.
► Two subjects carried a heterozygous GNRHR mutation, Q106R or R262Q, also present in controls with similar frequency.
► None of the subjects carried mutation(s) in FGFR1, PROK2, PROKR2, TAC3 or TACR3.
► It is unlikely that mutations in these genes would significantly contribute to the prevalence of isolated cryptorchidism.