Xing-Wu Wu1, Pei-Pei Liu1,2, Yang Zou2,3, Ding-Fei Xu1, Zhi-Qin Zhang1, Li-Yun Cao1,2, Lei-Zhen Xia1, Jia-Lv Huang1, Jia Chen1, Cai-Lin Xin1, Zhi-Hui Huang1, Jun Tan4,5, Qiong-Fang Wu6, Zeng-Ming Li7. 1. Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, 330006, People's Republic of China. 2. JXHC Key Laboratory of Fertility Preservation, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, 330006, People's Republic of China. 3. Central Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, 330006, People's Republic of China. 4. Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, 330006, People's Republic of China. tanjun561127@163.com. 5. JXHC Key Laboratory of Fertility Preservation, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, 330006, People's Republic of China. tanjun561127@163.com. 6. Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, 330006, People's Republic of China. wuqiongfang898@sina.com. 7. JXHC Key Laboratory of Fertility Preservation, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, 330006, People's Republic of China. lizhengming@163.com.
Abstract
PURPOSE: Oocyte death is a severe clinical phenotype that causes female infertility and recurrent in vitro fertilization and intracytoplasmic sperm injection failure. We aimed to identify pathogenic variants in a female infertility patient with oocyte death phenotype. METHODS: Sanger sequencing was performed to screen PANX1 variants in the affected patient. Western blot analysis was used to check the effect of the variant on PANX1 glycosylation pattern in vitro. RESULTS: We identified a novel PANX1 variant (NM_015368.4 c.86G > A, (p. Arg29Gln)) associated with the phenotype of oocyte death in a non-consanguineous family. This variant displayed an autosomal dominant inheritance pattern with reduced penetrance. Western blot analysis confirmed that the missense mutation of PANX1 (c.86G > A) altered the glycosylation pattern in HeLa cells. Moreover, the mutation effects on the function of PANX1 were weaker than recently reported variants. CONCLUSION: Our findings expand the inheritance pattern of PANX1 variants to an autosomal dominant mode with reduced penetrance and enrich the variational spectrum of PANX1. These results help us to better understand the genetic basis of female infertility with oocyte death.
PURPOSE: Oocyte death is a severe clinical phenotype that causes female infertility and recurrent in vitro fertilization and intracytoplasmic sperm injection failure. We aimed to identify pathogenic variants in a female infertility patient with oocyte death phenotype. METHODS: Sanger sequencing was performed to screen PANX1 variants in the affected patient. Western blot analysis was used to check the effect of the variant on PANX1 glycosylation pattern in vitro. RESULTS: We identified a novel PANX1 variant (NM_015368.4 c.86G > A, (p. Arg29Gln)) associated with the phenotype of oocyte death in a non-consanguineous family. This variant displayed an autosomal dominant inheritance pattern with reduced penetrance. Western blot analysis confirmed that the missense mutation of PANX1 (c.86G > A) altered the glycosylation pattern in HeLa cells. Moreover, the mutation effects on the function of PANX1 were weaker than recently reported variants. CONCLUSION: Our findings expand the inheritance pattern of PANX1 variants to an autosomal dominant mode with reduced penetrance and enrich the variational spectrum of PANX1. These results help us to better understand the genetic basis of female infertility with oocyte death.
Authors: Anas M Alazami; Salma M Awad; Serdar Coskun; Saad Al-Hassan; Hadia Hijazi; Firdous M Abdulwahab; Coralie Poizat; Fowzan S Alkuraya Journal: Genome Biol Date: 2015-11-05 Impact factor: 13.583
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