Premium
Cytogenetic signatures of recurrent pregnancy losses
Author(s) -
Yatsenko Svetlana A.,
QuesadaCandela Cristina,
Saller Devereux N.,
Beck Stacy,
Jaffe Ronald,
Kostadinov Stefan,
Yanowitz Judith,
Rajkovic Aleksandar
Publication year - 2021
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.5838
Subject(s) - nondisjunction , biology , genetics , aneuploidy , etiology , chromosome , offspring , meiosis , cohort , genome instability , chromosome instability , fetus , pregnancy , gene , medicine , dna , dna damage
Objectives To investigate the incidence of chromosomal abnormalities in the products of conception (POC) of patients with spontaneous miscarriages (SM) and with recurrent pregnancy losses (RPL) and to determine biological mechanisms contributing to RPL. Methods During a 20‐year period, 12 096 POC samples underwent classical chromosome analysis. Cytogenetic findings were compared between the SM and RPL cohorts. Results Analysis of RPL cohort has identified an increased incidence of inherited and de novo structural chromosome abnormalities, recurrent polyploid conceptions, and complex mosaic alterations. These abnormalities are the signature of genomic instability, posing a high risk of genetic abnormalities to offspring independent of maternal age. Predominance of male conceptions in the RPL cohort points toward an X‐linked etiology and gender‐specific intolerance for certain genetic abnormalities. Conclusions Our study showed several possible genetic etiologies of RPL, including parental structural chromosome rearrangements, predisposition to meiotic nondisjunction, and genomic instability. Loss of karyotypically normal fetuses might be attributed to defects in genes essential for fetal development, as well as aberrations affecting the X chromosome. Molecular studies of parental and POC genomes will help to identify inherited defects in genes involved in meiotic divisions and DNA repair to confirm our hypotheses, and to discover novel fetal‐essential genes.