Genetic analysis of first-trimester miscarriages with a combination of cytogenetic karyotyping, microsatellite genotyping and arrayCGH

• Published in: Clinical genetics Vol. 75; no. 2; pp. 133 - 140
• Main Authors: Zhang, Y-X, Zhang, Y-P, Gu, Y, Guan, F-J, Li, S-L, Xie, J-S, Shen, Y, Wu, B-L, Ju, W, Jenkins, EC, Brown, WT, Zhong, N
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-02-2009; Wiley-Blackwell
• Subjects: Abortion, Spontaneous - diagnosis; Abortion, Spontaneous - genetics; arrayCGH; Asian people; Biological and medical sciences; Chinese population; chromosome abnormality; Comparative Genomic Hybridization; comprehensive genetic study; Cytogenetics; deletion and duplication; Diseases of mother, fetus and pregnancy; Female; first trimester; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; genetic counseling; Genetic testing; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Gynecology. Andrology. Obstetrics; Humans; Karyotyping; Medical genetics; Medical sciences; microsatellite; Microsatellite Repeats - genetics; Miscarriage; Molecular and cellular biology; Pregnancy; Pregnancy Trimester, First - genetics; Pregnancy. Fetus. Placenta; Prenatal care; Prenatal Diagnosis - methods; Risk factors; Asia; China; Chromosomal aberration; Human; comprehensive genetic study; Pregnancy disorders; arrayCGH; deletion and duplication; miscarriage; Genotype; First trimester; Abortion; chromosome abnormality; Genetic counseling; Microsatellite DNA; Cytogenetics; Deletion; Chinese population; microsatellite; Abnormal chromosome; Genetics; Chromosome duplication; Karyotype
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2008.01131.x

Miscarriage is the spontaneous loss of an embryo or fetus before the 20th week of pregnancy. Most miscarriages occur before the end of the first trimester (<13 weeks). Although many risk factors relate to this occurrence, genetic factors play the most important role. Chromosomal abnormalities, including both numerical and structural anomalies, underlie the majority of miscarriages. In this study, we employed a comprehensive approach using cytogenetic karyotyping, polymerase chain reaction (PCR)‐based genotyping, and microarray‐based comparative genomic hybridization (arrayCGH) in combination to analyze chromosomal profiles of 115 first‐trimester miscarriages of Chinese women. Seventy cases (61%) were found to have chromosomal anomalies, of which 90% were numerical and 10% were structural. Cytogenetic karyotyping identified 78.6% (55/70), PCR assays 2.9% (2 triploids), and arrayCGH 18.6% (13/70) of the anomalies. In this study, a microdeletion of 108 kb and four microduplications sizing from 300 to 1460 kb were observed. An advantage of using this combination approach is that microsatellite genotyping and arrayCGH can be accomplished in spite of culture failure and maternal cell contamination. In addition, arrayCGH can detect submicroscopic chromosomal anomalies and gene dosage alterations.