Investigation of Chromosomal Abnormalities and Microdeletion/ Microduplication(s) in Fifty Iranian Patients with Multiple Congenital Anomalies

Mohammadzadeh, Akbar; Akbaroghli, Susan; Aghaei-Moghadam, Ehsan; Mahdieh, Nejat; Badv, Reza Shervin; Jamali, Payman; Kariminejad, Roxana; Chavoshzadeh, Zahra; Ghasemi Firouzabadi, Saghar; Mansour Ghanaie, Roxana; Nozari, Ahoura; Banihashemi, Sussan; Hadipour, Fatemeh; Hadipour, Zahra; Kariminejad, Ariana; Najmabadi, Hossein; Shafeghati, Yousef; Behjati, Farkhondeh

doi:10.22074/cellj.2019.6053

Investigation of Chromosomal Abnormalities and Microdeletion/ Microduplication(s) in Fifty Iranian Patients with Multiple Congenital Anomalies

Document Type : Original Article

Authors

¹ Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

² Pediatric Neurology Research Center, Mofid Children’s Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;Clinical Genetics Division, Mofid Children’s Hospital, Faculty of Med

³ 4Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

⁴ 5Cardiogenetic Research Laboratory, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

⁵ 6Genetic Counseling Center, Shahroud Welfare Organization, Shahroud, Iran

⁶ 7Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran

⁷ 8Department of Immunology and Allergy, Mofid Children’s Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;9Pediatric Infections Research Center, Research Institute for Childre

⁸ 9Pediatric Infections Research Center, Research Institute for Children’s Health, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

⁹ 0Sarem Fertility and Infertility Research Center (SAFIR), Sarem Women’s Hospital, Tehran, Iran;Sarem Cell Research Center (SCRC), Sarem Women’s Hospital, Tehran, Iran

¹⁰ Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran;7Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran

¹¹ Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran;0Sarem Fertility and Infertility Research Center (SAFIR), Sarem Women’s Hospital, Tehran, Iran;Sarem Cell Research Center (SCRC), S

10.22074/cellj.2019.6053

Abstract

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.

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