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Objective: Major birth defects are inborn structural or functional anomalies with long-term disability and adverse impacts on individuals, families, health-care systems, and societies. Approximately 20% of birth defects are due to chromosomal and genetic conditions. Inspired by the fact that neonatal deaths are caused by birth defects in about 20 and 10% of cases in Iran and worldwide respectively, we conducted the present study to unravel the role of chromosome abnormalities, including microdeletion/microduplication(s), in multiple congenital abnormalities in a number of Iranian patients. Materials and Methods: In this descriptive cross-sectional study, 50 sporadic patients with Multiple Congenital Anomalies (MCA) were selected. The techniques employed included conventional karyotyping, fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and array comparative genomic hybridisation (array-CGH), according to the clinical diagnosis for each patient. Results: Chromosomal abnormalities and microdeletion/microduplication(s) were observed in eight out of fifty patients (16%). The abnormalities proved to result from the imbalances in chromosomes 1, 3, 12, and 18 in four of the patients. However, the other four patients were diagnosed to suffer from the known microdeletions of 22q11.21, 16p13.3, 5q35.3, and 7q11.23. Conclusion: In the present study, we report a patient with 46,XY, der(18)[12]/46,XY, der(18), +mar[8] dn presented with MCA associated with hypogammaglobulinemia. Given the patient's seemingly rare and highly complex chromosomal abnormality and the lack of any concise mechanism presented in the literature to justify the case, we hereby propose a novel mechanism for the formation of both derivative and ring chromosome 18. In addition, we introduce a new 12q abnormality and a novel association of an Xp22.33 duplication with 1q43q44 deletion syndrome. The phenotype analysis of the patients with chromosome abnormality would be beneficial for further phenotype-genotype correlation studies. [ABSTRACT FROM AUTHOR]

Background: Pregnancy loss affects 10%-15% of pregnancies and is caused by several factors, maternal and fetal. Most common cause is chromosomal aneuploidy and has traditionally been detected by karyotyping product of conception and/or fetal tissue. In recent years, array comparative genomic hybridization (a-CGH) has been used because of its higher detection and lower failure rates., Methods: DNA was extracted from 1625 products of abortion or fetal tissue. In 1,104 cases both quantitative fluorescent-polymerase chain reaction (QF-PCR) and a-CGH, and in 521 cases only a-CGH, was performed., Results: The detection rate using QF-PCR and a-CGH is 20% compared to 12.7%, overall, and 15.7%, excluding failed samples, by karyotypes in our center. QF-PCR and a-CGH failed in 1.9% of cases, while the failure rate for karyotypes was 20.1%. The difference of detection and failure rates is significant (p-value < 0.001 and p-value < 0.001 respectively). Unexpectedly we also found a significant difference in frequency of imbalances in related versus unrelated couples. (χ 2  = 11.4926, p-value < 0.001)., Conclusion: It is highly likely that the pregnancy loss in consanguineous couples is caused by other genetic and immune mechanisms. It is plausible that, through the same mechanism by which single gene disorders have a higher prevalence of manifesting disease in consanguineous couples, they can cause lethal genetic disorders leading to pregnancy loss and intra-uterine fetal death (IUFD) in these couples. Our findings suggest that this is a matter for further study as it will greatly influence the approach to counseling and managing consanguineous couples with pregnancy loss., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)