• PMID: 28464846
• Gene Name: EGR4
• Condition: Spermatogenesis impairement
• Association: Associated
• Mutation: rs771189047, rs561568849, rs763487015, rs546250227, rs115948271, rs528939702, rs7558708, rs2229294, [c.65_66InsG (p. Cys23Leufs*37), c.236C?>?T (p. Pro79Leu), c.1294G?>?T (p. Val432Leu)], [c.1230G?>?A (p. Thr410)], c.214C?>?A (p. Arg72Ser), c.236C?>?T (p
• Population size: 442
• Population details: 442 (170 Korean men with impaired spermatogenesis and 272 normal controls)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Spermatogenesis impairement

Sequence variations of the EGR4 gene in Korean men with spermatogenesis impairment

Sung SR, Song SH, Kang KM, Park JE, Nam YJ, Shin YJ, Cha DH, Seo JT, Yoon TK, Shim SH.

BACKGROUND: Egr4 is expressed in primary and secondary spermatocytes in adult mouse testes and has a crucial role in regulating germ cell maturation. The functional loss of Egr4 blocks spermatogenesis, significantly reducing the number of spermatozoa that are produced. In this study, we examined whether EGR4 variants are present in Korean men with impaired spermatogenesis. METHODS: A total 170 Korean men with impaired spermatogenesis and 272 normal controls were screened. The coding regions including exon-intron boundaries of EGR4 were sequenced by PCR-direct sequencing method. RESULTS: We identified eight sequence variations in the coding region and 3'-UTR regions of the EGR4 gene. Four were nonsynonymous variants (rs771189047, rs561568849, rs763487015, and rs546250227), three were synonymous variants (rs115948271, rs528939702, and rs7558708), and one variant (rs2229294) was localized in the 3'-UTR. Three nonsynonymous variants [c.65_66InsG (p. Cys23Leufs*37), c.236C > T (p. Pro79Leu), c.1294G > T (p. Val432Leu)] and one synonymous variant [c.1230G > A (p. Thr410)] were not detected in controls. To evaluate the pathogenic effects of nonsynonymous variants, we used seven prediction methods. The c.214C > A (p. Arg72Ser) and c.236C > T (p. Pro79Leu) variants were predicted as "damaging" by SIFT and SNAP(2). The c.65_66insG (p. Cys23Leufs*37) variants were predicted as "disease causing" by Mutation Taster, SNPs &GO and SNAP(2). The c.867C > G (p. Leu289) variants were predicted as "disease causing" only by Mutation Taster. CONCLUSION: To date, this study is the first to screen the EGR4 gene in relation to male infertility. However, our findings did not clearly explain how nonsynonymous EGR4 variations affect spermatogenesis. Therefore, further studies are required to validate the functional impact of EGR4 variations on spermatogenesis. FAU - Sung, Se Ra AU - Sung SR AD - Genetics Laboratory, Fertility Center of CHA Gangnam Medical Center, Seoul, South Korea. FAU - Song, Seung Hun AU - Song SH AD - Department of Urology, CHA Gangnam Medical Center, Seoul, South Korea. FAU - Kang, Kyung Min AU - Kang KM AD - Genetics Laboratory, Fertility Center of CHA Gangnam Medical Center, Seoul, South Korea. FAU - Park, Ji Eun AU - Park JE AD - Genetics Laboratory, Fertility Center of CHA Gangnam Medical Center, Seoul, South Korea. FAU - Nam, Yeo Jung AU - Nam YJ AD - Department of Biomedical Science, College of Life Science, CHA University, Seoul, South Korea. FAU - Shin, Yun-Jeong AU - Shin YJ AD - Genetics Laboratory, Fertility Center of CHA Gangnam Medical Center, Seoul, South Korea. FAU - Cha, Dong Hyun AU - Cha DH AD - Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, Seoul, South Korea. FAU - Seo, Ju Tae AU - Seo JT AD - Department of Urology, Cheil General Hospital, Seoul, South Korea. FAU - Yoon, Tae Ki AU - Yoon TK AD - Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, Seoul, South Korea.