title: Is germline transmission of MAD2 gene deletion associated with human fetal loss?
abstract: The spindle assembly checkpoint (SAC) monitors proper attachment of spindles to the kinetochore during mitotic and meiotic cell divisions and thus prevents aneuploidy. Chromosomal aneuploidy has been found to be associated with pregnancy loss and birth defects. Mad2 is one of the critical molecules of SAC. Deregulated Mad2 expression has been found to be associated with defective SAC-mediated abnormal meiotic progression in cell studies using animal models. Whether mutation in MAD2L1 is associated with the loss of Mad2 expression in aborted human fetuses is unknown. In this study, a correlation between aneuploidy and MAD2 defect was examined in primary fibroblast cultures obtained from abortuses. We report three trisomic abortuses with undetectable Mad2 expression. Further, quantitative real-time PCR revealed copy number deletion of MAD2 gene in these fetuses. Analysis of parental DNA samples available from two families revealed copy number loss of the same gene, suggesting Mendelian inheritance of MAD2 deletion. This germline transmission of exonic deletion of MAD2 is possibly associated with its loss of expression resulting in abnormal SAC function, subsequent aneuploidy and pregnancy loss.
authors.affiliation: Cancer Biology and Inflammatory Disorder Division,  CSIR, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700032,  India.
authors.forename: Somsubhra
authors.initials: S
authors.lastname: Nath
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Moghe
authors.forename: Abhishek
authors.initials: A
authors.lastname: Chowdhury
authors.forename: Koumudi
authors.initials: K
authors.lastname: Godbole
authors.forename: Girish
authors.initials: G
authors.lastname: Godbole
authors.forename: Manisha
authors.initials: M
authors.lastname: Doiphode
authors.forename: Susanta
authors.initials: S
authors.lastname: Roychoudhury
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics*; D005091:Exons; D005260:Female; D005333:Fetus; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D018628:Gene Dosage; D015870:Gene Expression; D018095:Germ-Line Mutation; D006801:Humans; D007621:Karyotyping; D018386:Kinetochores / Q000378:metabolism / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics*; D064246:Mad2 Proteins; D008540:Meiosis / Q000235:genetics; D011247:Pregnancy; D061251:Primary Cell Culture; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics*; D008941:Spindle Apparatus / Q000378:metabolism / Q000473:pathology; D014314:Trisomy / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins