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


Akbar Mohammadzadeh, M.D, 1Susan Akbaroghli, M.D, 2,3Ehsan Aghaei-Moghadam, M.D, 4Nejat Mahdieh, Ph.D, 5Reza Shervin Badv, M.D, 4Payman Jamali, M.D, 6Roxana Kariminejad, Ph.D, 7Zahra Chavoshzadeh, M.D, 8,9Saghar Ghasemi Firouzabadi, Ph.D, 1Roxana Mansour Ghanaie, M.D, 9Ahoura Nozari, Ph.D, 1Sussan Banihashemi, B.Sc, 1Fatemeh Hadipour, M.D, 10,11Zahra Hadipour, M.D, 10,11Ariana Kariminejad, M.D, 7Hossein Najmabadi, Ph.D, 1,7Yousef Shafeghati, M.D, 10,11Farkhondeh Behjati, Ph.D, 1,10,11,*
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
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 Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
Cardiogenetic Research Laboratory, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Genetic Counseling Center, Shahroud Welfare Organization, Shahroud, Iran
Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran
Department of Immunology and Allergy, Mofid Children’s Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Pediatric Infections Research Center, Research Institute for Children’s Health, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Sarem Fertility and Infertility Research Center (SAFIR), Sarem Women’s Hospital, Tehran, Iran
Sarem Cell Research Center (SCRC), Sarem Women’s Hospital, Tehran, Iran
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
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 Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
Cardiogenetic Research Laboratory, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Genetic Counseling Center, Shahroud Welfare Organization, Shahroud, Iran
Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran
Department of Immunology and Allergy, Mofid Children’s Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Pediatric Infections Research Center, Research Institute for Children’s Health, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Sarem Fertility and Infertility Research Center (SAFIR), Sarem Women’s Hospital, Tehran, Iran
Sarem Cell Research Center (SCRC), Sarem Women’s Hospital, Tehran, Iran
*Corresponding Address: P.O.Box: 1985713871 Genetics Research Center University of Social Welfare and Rehabilitation Sciences Daneshjoo Blvd Koodakyar St Evin Tehran Iran Email:f_behjati@uswr.ac.ir
The Cell Journal (Yakhteh) is an open access journal which means the articles are freely available online for any individual author to download and use the providing address. The journal is licensed under a Creative Commons Attribution-Non Commercial 3.0 Unported License which allows the author(s) to hold the copyright without restrictions that is permitting unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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. Investigation of Chromosomal Abnormalities and Microdeletion/ Microduplication(s) in Fifty Iranian Patients with Multiple Congenital Anomalies. Cell J. 2019; 21(3): 337-349.

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.