• Alexander N Yatsenko, Andrew P Georgiadis, Albrecht Röpke, Andrea J Berman, Thomas Jaffe, Marta Olszewska, Birgit Westernströer, Joseph Sanfilippo, Maciej Kurpisz, Aleksandar Rajkovic, Svetlana A Yatsenko, Sabine Kliesch, Stefan Schlatt, and Frank Tüttelmann.
• From the Departments of Obstetrics, Gynecology, and Reproductive Sciences (A.N.Y., A.P.G., J.S., A. Rajkovic, S.A.Y.) and Urology (T.J.), University of Pittsburgh School of Medicine, and the Department of Biological Sciences, University of Pittsburgh, Kenneth P. Dietrich School of Arts and Sciences (A.J.B.) - all in Pittsburgh; the Institute of Human Genetics (A. Röpke, F.T.) and Center of Reproductive Medicine and Andrology (B.W., S.K., S.S.), University of Münster, Münster, Germany; and the Department of Reproductive Biology and Stem Cells, Institute of Human Genetics, Polish Academy of Sciences, Poznań (M.O., M.K.).
• N. Engl. J. Med.. 2015 May 28;372(22):2097-107.

BackgroundThe genetic basis of nonobstructive azoospermia is unknown in the majority of infertile men.MethodsWe performed array comparative genomic hybridization testing in blood samples obtained from 15 patients with azoospermia, and we performed mutation screening by means of direct Sanger sequencing of the testis-expressed 11 gene (TEX11) open reading frame in blood and semen samples obtained from 289 patients with azoospermia and 384 controls.ResultsWe identified a 99-kb hemizygous loss on chromosome Xq13.2 that involved three TEX11 exons. This loss, which was identical in 2 patients with azoospermia, predicts a deletion of 79 amino acids within the meiosis-specific sporulation domain SPO22. Our subsequent mutation screening showed five novel TEX11 mutations: three splicing mutations and two missense mutations. These mutations, which occurred in 7 of 289 men with azoospermia (2.4%), were absent in 384 controls with normal sperm concentrations (P=0.003). Notably, five of those TEX11 mutations were detected in 33 patients (15%) with azoospermia who received a diagnosis of azoospermia with meiotic arrest. Meiotic arrest in these patients resembled the phenotype of Tex11-deficient male mice. Immunohistochemical analysis showed specific cytoplasmic TEX11 expression in late spermatocytes, as well as in round and elongated spermatids, in normal human testes. In contrast, testes of patients who had azoospermia with TEX11 mutations had meiotic arrest and lacked TEX11 expression.ConclusionsIn our study, hemizygous TEX11 mutations were a common cause of meiotic arrest and azoospermia in infertile men. (Funded by the National Institutes of Health and others.).

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