2. Academic Validation
  3. Mutant ZP1 in familial infertility

Mutant ZP1 in familial infertility

  • N Engl J Med. 2014 Mar 27;370(13):1220-6. doi: 10.1056/NEJMoa1308851.
Hua-Lin Huang 1,  Chao Lv,  Ying-Chun Zhao,  Wen Li,  Xue-Mei He,  Ping Li,  Ai-Guo Sha,  Xiao Tian,  Christopher J Papasian,  Hong-Wen Deng,  Guang-Xiu Lu,  Hong-Mei Xiao
Affiliations

Affiliation

  • 1 From the Institute of Reproduction and Stem Cell Engineering, Central South University (H.-L.H., C.L., W.L., G.-X.L., H.-M.X.), Reproductive and Genetic Hospital of CITIC-Xiangya (W.L., G.-X.L., H.-M.X.), and the First High School of Changsha (X.T.), Changsha, and Xiamen Maternal and Child Health Care Hospital (X.-M.H., P.L.) and PLA Hospital No.174 (A.-G.S.), Xiamen - all in China; the Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans (H.-L.H., Y.-C.Z., H.-W.D.); and the School of Medicine, University of Missouri-Kansas City, Kansas City (C.J.P.).
PMID: 24670168 DOI: 10.1056/NEJMoa1308851
Abstract

The human zona pellucida is composed of four glycoproteins (ZP1, ZP2, ZP3, and ZP4) and has an important role in reproduction. Here we describe a form of infertility with an autosomal recessive mode of inheritance, characterized by abnormal eggs that lack a zona pellucida. We identified a homozygous frameshift mutation in ZP1 in six family members. In vitro studies showed that defective ZP1 proteins and normal ZP3 proteins colocalized throughout the cells and were not expressed at the cell surface, suggesting that the aberrant ZP1 results in the sequestration of ZP3 in the cytoplasm, thereby preventing the formation of the zona pellucida around the oocyte.

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