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

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

doi:10.22074/cellj.2019.6053

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

Cell J. 2019 Oct;21(3):337-349. doi: 10.22074/cellj.2019.6053. Epub 2019 Jun 15.

Authors

Akbar Mohammadzadeh¹, Susan Akbaroghli^{2

3}, Ehsan Aghaei-Moghadam⁴, Nejat Mahdieh⁵, Reza Shervin Badv⁴, Payman Jamali⁶, Roxana Kariminejad⁷, Zahra Chavoshzadeh^{8

9}, Saghar Ghasemi Firouzabadi¹, Roxana Mansour Ghanaie⁹, Ahoura Nozari¹, Sussan Banihashemi¹, Fatemeh Hadipour^{10

11}, Zahra Hadipour^{10

11}, Ariana Kariminejad⁷, Hossein Najmabadi^{1

7}, Yousef Shafeghati^{10

11}, Farkhondeh Behjati^{12

10

11}

Affiliations

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.
³ Clinical Genetics Division, Mofid Children's Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁴ Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Cardiogenetic Research Laboratory, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
⁶ Genetic Counseling Center, Shahroud Welfare Organization, Shahroud, Iran.
⁷ Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
⁸ Department of Immunology and Allergy, Mofid Children's Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁹ Pediatric Infections Research Center, Research Institute for Children's Health, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
¹⁰ Sarem Fertility and Infertility Research Center (SAFIR), Sarem Women's Hospital, Tehran, Iran.
¹¹ Sarem Cell Research Center (SCRC), Sarem Women's Hospital, Tehran, Iran.
¹² Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.Electronic Address: f_behjati@uswr.ac.ir.

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.

Keywords: Array Comparative Genomic Hybridization; Chromosomal Abnormalities; Congenital Abnormalities; Microdeletions; Multiplex Ligation-Dependent Probe Amplification.