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Towards Solving the Genetic Diagnosis Odyssey in Iranian Patients With Congenital Anomalies Publisher



Vaseghi P1, 2 ; Habibi L3 ; Neidich JA4, 5 ; Cao Y4 ; Fattahi N3 ; Rashidinezhad R3 ; Salehnezhad T3 ; Dalili H6, 7 ; Rahimi Sharbaf F8 ; Zarkesh MR9 ; Malekian M3 ; Mokhberdezfuli M3, 10 ; Mehrtash A3 ; Ardeshirdavani A11 Show All Authors
Authors
  1. Vaseghi P1, 2
  2. Habibi L3
  3. Neidich JA4, 5
  4. Cao Y4
  5. Fattahi N3
  6. Rashidinezhad R3
  7. Salehnezhad T3
  8. Dalili H6, 7
  9. Rahimi Sharbaf F8
  10. Zarkesh MR9
  11. Malekian M3
  12. Mokhberdezfuli M3, 10
  13. Mehrtash A3
  14. Ardeshirdavani A11
  15. Kariminejad R12
  16. Ghorbansabagh V7, 13
  17. Sadeghimoghadam P7, 13
  18. Naddaf A7, 13
  19. Esmaeilnia Shirvany T7, 13
  20. Mosayebi Z7, 13
  21. Sahebdel B8
  22. Golshahi F8
  23. Shirazi M8
  24. Shamel S9
  25. Moeini R9
  26. Heidari A14
  27. Daneshmand MA15
  28. Ghasemi R4
  29. Akrami SM1
  30. Rashidinezhad A13, 16
Show Affiliations
Authors Affiliations
  1. 1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran
  3. 3. Ronash Medical Genetics Laboratory, Tehran, Iran
  4. 4. Department of Pathology & Immunology, Division of Laboratory & Genomic Medicine, Washington University School of Medicine, St. Louis, MO, United States
  5. 5. Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
  6. 6. Breastfeeding Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Pediatrics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Obstetrics and Gynecology, School of Medicine, Yas Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Department of Neonatology, Yas Hospital Complex, Tehran university of medical sciences, Tehran, Iran
  10. 10. Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  11. 11. Cimorgh Medical IT Solutions, Tehran, Iran
  12. 12. Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran
  13. 13. Maternal, Fetal and Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  14. 14. Sana Medical Genetics Laboratory, Ghazvin, Iran
  15. 15. Former teacher of Pathology, Arak Medical University, Arak, Iran
  16. 16. Genetics Ward, Yas Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

Source: European Journal of Human Genetics Published:2024


Abstract

Understanding the underlying causes of congenital anomalies (CAs) can be a complex diagnostic journey. We aimed to assess the efficiency of exome sequencing (ES) and chromosomal microarray analysis (CMA) in patients with CAs among a population with a high fraction of consanguineous marriage. Depending on the patient’s symptoms and family history, karyotype/Quantitative Fluorescence- Polymerase Chain Reaction (QF-PCR) (n = 84), CMA (n = 81), ES (n = 79) or combined CMA and ES (n = 24) were performed on 168 probands (66 prenatal and 102 postnatal) with CAs. Twelve (14.28%) probands were diagnosed by karyotype/QF-PCR and seven (8.64%) others were diagnosed by CMA. ES findings were conclusive in 39 (49.36%) families, and 61.90% of them were novel variants. Also, 64.28% of these variants were identified in genes that follow recessive inheritance in CAs. The diagnostic rate (DR) of ES was significantly higher than that of CMA in children from consanguineous families (P = 0·0001). The highest DR by CMA was obtained in the non-consanguineous postnatal subgroup and by ES in the consanguineous prenatal subgroup. In a population that is highly consanguineous, our results suggest that ES may have a higher diagnostic yield than CMA and should be considered as the first-tier test in the evaluation of patients with congenital anomalies. © 2024, The Author(s), under exclusive licence to European Society of Human Genetics.
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