Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021359 (infertility)
 26,075 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Globozoospermia has been reported to be a rare but severe causation of male infertility, which results from the failure of acrosome biogenesis and sperm head shaping. Variants of dpy-19-like 2 (DPY19L2) are highly related to globozoospermia, but related investigations have been mainly performed in patients from Western countries. Here, we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations, as revealed by whole-exome sequencing. Patient 3 (P3) contained a heterozygous variant (c.2126+5G>A), P6 contained a homozygous nonsense mutation (c.1720C>T, p.Arg574*), P8 contained compound heterozygous variants (c.1182-1184delATC, p.Leu394_Ser395delinsPhe; c.368A>T, p.His123Arg), and P9 contained a heterozygous variant (c.1182-1184delATCTT, frameshift). We also reported intracytoplasmic sperm injection (ICSI) outcomes in the related patients, finding that ICSI followed by assisted oocyte activation (AOA) with calcium ionophore achieved high rates of live births. In summary, the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.
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PMID:Novel DPY19L2 variants in globozoospermic patients and the overcoming this male infertility. 3033 25

Globozoospermia is a form of teratozoospermia characterized by round-headed spermatozoa and lack of acrosome. These spermatozoa cannot penetrate the zona pellucida of the oocyte, resulting in unsuccessful fertilization and infertility. When intracytoplasmic sperm injection is performed, the fertilization rate tends to be low. Until now, the causes of this disorder remain to be elucidated; however, mutations of some genes segregating on an autosomal recessive mode have been associated with this infertile condition. DPY19L2 (dpy-19-like 2 [Caenorhabditis elegans]) codes for a transmembrane protein expressed predominantly in spermatids, with specific localization limited to the internal nuclear membrane. Genetic defects in the DPY19L2 gene have been demonstrated the most frequent genetic cause of globozoospermia; however, intracellular molecular pathways related to its encoded protein are largely unknown. In this issue of Proteomics Clinical Applications, Guo and co-workers investigate the proteome of gloobozoospermic spermatozoa. The authors identified 491 proteins that are differentially expressed in globozoospermia (370 are upregulated and 121 are downregulated in DPY19L2-deficient globozoospermic sperm). Notably, the molecular defects identified by the authors are closely related to biological processes involved in acrosome formation, chromatin composition, sperm-egg binding, and fertilization.
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PMID:Proteomic Research of Molecular Defects in Globozoospermia. 3142 56