Towards solving the genetic diagnosis odyssey in Iranian patients with congenital anomalies

Parisa Vaseghi, Laleh Habibi, Julie A. Neidich, Yang Cao, Neda Fattahi, Ramin Rashidi-Nezhad, Tayebeh Salehnezhad, Hossein Dalili, Fatemeh Rahimi Sharbaf, Mohammad Reza Zarkesh, Mahtash Malekian, Mahdieh Mokhberdezfuli, Amirhosein Mehrtash, Amin Ardeshirdavani, Roxana Kariminejad, Vafa Ghorbansabagh, Parvane Sadeghimoghadam, Amir Naddaf, Tahereh Esmaeilnia Shirvany, Ziba MosayebiBehrokh Sahebdel, Fatemeh Golshahi, Mahboobeh Shirazi, Shirin Shamel, Roksana Moeini, Abolfazl Heidari, Mohammad Ali Daneshmand, Reza Ghasemi, Seyed Mohammad Akrami, Ali Rashidi-Nezhad

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish
JournalEuropean Journal of Human Genetics
StateAccepted/In press - 2024


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