title: Mutant ZP1 in familial infertility.
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.
authors.affiliation: 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.).
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Huang
authors.forename: Chao
authors.initials: C
authors.lastname: Lv
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Zhao
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: He
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Sha
authors.forename: Xiao
authors.initials: X
authors.lastname: Tian
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
authors.forename: Guang-Xiu
authors.initials: GX
authors.lastname: Lu
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Xiao
mesh_terms: D000328:Adult; D002681:China; D004252:DNA Mutational Analysis; D004527:Egg Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007247:Infertility, Female / Q000235:genetics* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010063:Ovum / Q000378:metabolism* / Q000473:pathology; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000072216:Zona Pellucida Glycoproteins
chemical_list: D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C000606514:ZP1 protein, human; C000606515:ZP2 protein, human; C000606517:ZP3 protein, human; D000072216:Zona Pellucida Glycoproteins