TY - JOUR
T1 - Towards solving the genetic diagnosis odyssey in Iranian patients with congenital anomalies
AU - Vaseghi, Parisa
AU - Habibi, Laleh
AU - Neidich, Julie A.
AU - Cao, Yang
AU - Fattahi, Neda
AU - Rashidi-Nezhad, Ramin
AU - Salehnezhad, Tayebeh
AU - Dalili, Hossein
AU - Rahimi Sharbaf, Fatemeh
AU - Zarkesh, Mohammad Reza
AU - Malekian, Mahtash
AU - Mokhberdezfuli, Mahdieh
AU - Mehrtash, Amirhosein
AU - Ardeshirdavani, Amin
AU - Kariminejad, Roxana
AU - Ghorbansabagh, Vafa
AU - Sadeghimoghadam, Parvane
AU - Naddaf, Amir
AU - Esmaeilnia Shirvany, Tahereh
AU - Mosayebi, Ziba
AU - Sahebdel, Behrokh
AU - Golshahi, Fatemeh
AU - Shirazi, Mahboobeh
AU - Shamel, Shirin
AU - Moeini, Roksana
AU - Heidari, Abolfazl
AU - Daneshmand, Mohammad Ali
AU - Ghasemi, Reza
AU - Akrami, Seyed Mohammad
AU - Rashidi-Nezhad, Ali
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to European Society of Human Genetics 2024.
PY - 2024/10
Y1 - 2024/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85183380309&partnerID=8YFLogxK
U2 - 10.1038/s41431-024-01533-x
DO - 10.1038/s41431-024-01533-x
M3 - Article
C2 - 38278869
AN - SCOPUS:85183380309
SN - 1018-4813
VL - 32
SP - 1238
EP - 1249
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 10
ER -