Hum. Reprod. Advance Access originally published online on July 1, 2008
Human Reproduction 2008 23(10):2380-2384; doi:10.1093/humrep/den247
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Homozygous mutation in the prokineticin-receptor2 gene (Val274Asp) presenting as reversible Kallmann syndrome and persistent oligozoospermia: Case Report
1 Department of Clinical and Experimental Medicine and Surgery, Endocrinology and Medical Andrology Section, Seconda Università di Napoli, Build 16, Via Pansini 5, 80131 Napoli, Italy 2 Medical Genetics and CEINGE, Universita' Federico II, Napoli, Italy 3 Radiology Unit, Universita' Federico II, Napoli, Italy
4 Correspondence address. Tel/Fax: +39-0815666627; E-mail: antonio.sinisi{at}unina2.it
Prokineticin 2 (Prok2) or prokineticin-receptor2 (Prok-R2) gene mutations are associated with Kallmann syndrome (KS). We describe a new homozygous mutation of Prok-R2 gene in a man displaying KS with an apparent reversal of hypogonadism. The proband, offspring of consanguineous parents, presented at age 19 years with absent puberty, no sense of smell, low testosterone and gonadotrophin levels. Magnetic resonance imaging showed olfactory bulb absence. The patient achieved virilization and spermatogenesis with gonadotrophin administration. Two years after discontinuing hormonal therapy, he maintained moderate oligozoospermia and normal testosterone levels. Prok2 and Prok-R2 gene sequence analyses were performed. The proband had a homozygous mutation in Prok-R2 exon 2 that harbours the c.T820>A base substitution, causing the introduction of an aspartic acid in place of valine at position 274 (Val274Asp). His mother had the same mutation in heterozygous state. This report describes a novel homozygous mutation of Prok-R2 gene in a man with variant KS, underlying the role of Prok-R2 gene in the olfactory and reproductive system development in humans. Present findings indicate that markedly delayed activation of gonadotrophin secretion may occur in some KS cases with definite gene defects, and that oligozoospermia might result from a variant form of reversible hypogonadotrophic hypogonadism.
Key words: hypogonadotrophic hypogonadism/prokineticin-receptor2/anosmia/reversible Kallmann syndrome
These authors contributed equally to this work. Submitted on February 10, 2008; resubmitted on May 25, 2008; accepted on June 3, 2008.