Successful fertility restoration after allogeneic hematopoietic stem cell transplantation.

Objective: Myeloablative conditioning regimens given prior to hematopoietic stem cell transplantation (HSCT) frequently cause permanent sterility in men. In patients with sickle cell disease (SCD) we use a nonmyeloablative regimen with sirolimus, alemtuzumab, and low-dose total-body irradiation (300 centigrays) with gonadal shielding preceding allogeneic HSCT. We report here the restoration of azoospermia in a patient with SCD after allogeneic HSCT.

POTE protein, a cancer-testis antigen, is highly expressed in spermatids in human testis and is associated with apoptotic cells.

The POTE gene family encodes very closely related proteins that are highly expressed in testis and in many cancers. Recent studies indicate that the POTE proteins have a pro-apoptotic function. To examine if POTE is associated with cells that are undergoing apoptosis in testis, we determined the cellular location of POTE and of Cleaved Caspase-3 in testicular tissues from 26 azoospermic men.

The prevalence of digenic mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome.

Objective: To determine the prevalence of digenic mutations in patients with idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS).

Design: Molecular analysis of DNA in IHH/KS patients.

Setting: Academic medical center.

Nasal embryonic LHRH factor (NELF) mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome.

Objective: To determine if mutations in NELF, a gene isolated from migratory GnRH neurons, cause normosmic idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS).

Design: Molecular analysis correlated with phenotype.

Setting: Academic medical center.

WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome.

By defining the chromosomal breakpoint of a balanced t(10;12) translocation from a subject with Kallmann syndrome and scanning genes in its vicinity in unrelated hypogonadal subjects, we have identified WDR11 as a gene involved in human puberty. We found six patients with a total of five different heterozygous WDR11 missense mutations, including three alterations (A435T, R448Q, and H690Q) in WD domains important for β propeller formation and protein-protein interaction. In addition, we discovered that WDR11 interacts with EMX1, a homeodomain transcription factor involved in the development of olfactory neurons, and that missense alterations reduce or abolish this interaction.