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

Journal

European journal of human genetics : EJHG

ISSN: 1476-5438

Titre abrégé: Eur J Hum Genet

Pays: England

ID NLM: 9302235

Informations de publication

Date de publication:
26 Jan 2024

Historique:

received: 22 03 2023

accepted: 12 12 2023

revised: 23 11 2023

medline: 27 1 2024

pubmed: 27 1 2024

entrez: 26 1 2024

Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1038/s41431-024-01533-x PMID: 38278869

pubmed: 38278869

doi: 10.1038/s41431-024-01533-x

pii: 10.1038/s41431-024-01533-x

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Subventions

Organisme : Tehran University of Medical Sciences and Health Services (TUMS)

ID : 52367

Organisme : Tehran University of Medical Sciences and Health Services (TUMS)

ID : 52355

Informations de copyright

Références

World Health Organization. Congenital anomalies. Fact sheet N 370. Available at who int/mediacentre/factsheet/fs370/en. 2015.

Guide E. Instruction for the registration of congenital anomalies. Eurocat Cent Registry Dept Epidemiol, Cathol Univ Louvian, Bruss Pp. 1990;153:157.

Martínez‐Frías M, Bermejo E, Frias J. Pathogenetic classification of a series of 27,145 consecutive infants with congenital defects. Am J Med Genet. 2000;90:246–9.

doi: 10.1002/(SICI)1096-8628(20000131)90:3<246::AID-AJMG12>3.0.CO;2-Q pubmed: 10678664

Garne E, Dolk H, Loane M, Wellesley D, Barisic I, Calzolari E, et al. Paper 5: Surveillance of multiple congenital anomalies: implementation of a computer algorithm in European registers for classification of cases. Birth Defects Res Part A: Clin Mol Teratol. 2011;91:S44–50.

doi: 10.1002/bdra.20777

Dobrescu MA, Burada F, Cucu MG, Riza AL, Chelu G, Plesea RM, et al. Prenatal genetic counseling in congenital anomalies. congenital anomalies-from the embryo to the neonate: IntechOpen. 2018.

Zaidi S, Brueckner M. Genetics and genomics of congenital heart disease. Circulation Res. 2017;120:923–40.

doi: 10.1161/CIRCRESAHA.116.309140 pubmed: 28302740

Vivante A, Kohl S, Hwang D-Y, Dworschak GC, Hildebrandt F. Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans. Pediatr Nephrol. 2014;29:695–704.

doi: 10.1007/s00467-013-2684-4 pubmed: 24398540 pmcid: 4676405

Leslie EJ, Marazita ML, editors. Genetics of cleft lip and cleft palate. American Journal of Medical Genetics Part C: Seminars in Medical Genetics; 2013: Wiley Online Library.

Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86:749–64.

doi: 10.1016/j.ajhg.2010.04.006 pubmed: 20466091 pmcid: 2869000

Carss KJ, Hillman SC, Parthiban V, McMullan DJ, Maher ER, Kilby MD, et al. Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound. Hum Mol Genet. 2014;23:3269–77.

doi: 10.1093/hmg/ddu038 pubmed: 24476948 pmcid: 4030780

He M, Du L, Xie H, Zhang L, Gu Y, Lei T, et al. The added value of whole-exome sequencing for anomalous fetuses with detailed prenatal ultrasound and postnatal phenotype. Front Genet. 2021;12:627204.

doi: 10.3389/fgene.2021.627204 pubmed: 34367232 pmcid: 8340955

Vora NL, Powell B, Brandt A, Strande N, Hardisty E, Gilmore K, et al. Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges. Genet Med. 2017;19:1207.

doi: 10.1038/gim.2017.33 pubmed: 28518170 pmcid: 5675748

Hsu R-H, Lee C-H, Chien Y-H, Hwu P, Lee N-C. eP146: application of exome sequencing in patients of congenital anomalies with or without intellectual disability. Genet Med. 2022;24:S90.

doi: 10.1016/j.gim.2022.01.182

Weh E, Reis LM, Happ HC, Levin AV, Wheeler PG, David KL, et al. Whole exome sequence analysis of Peters anomaly. Hum Genet. 2014;133:1497–511.

doi: 10.1007/s00439-014-1481-x pubmed: 25182519 pmcid: 4395516

Srivastava S, Love-Nichols JA, Dies KA, Ledbetter DH, Martin CL, Chung WK, et al. Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genet Med. 2019;21:2413–21.

doi: 10.1038/s41436-019-0554-6 pubmed: 31182824 pmcid: 6831729

Manickam K, McClain MR, Demmer LA, Biswas S, Kearney HM, Malinowski J, et al. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23:2029–37.

doi: 10.1038/s41436-021-01242-6 pubmed: 34211152

Rashidi-Nezhad A, Fakhri L, Hantoush Zadeh S, Amini E, Sajjadian N, Hossein Zadeh P, et al. Evaluating the pre-, peri-and post-natal conditions of neonates affected by multiple congenital anomalies: a brief report. Tehran Univ Med J. 2013;70:659–64.

Network NBDP. Appendix 3.1. Birth defects descriptions for NBDPN core, recommended, and extended conditions. Guidelines for conducting birth defects surveillance Atlanta, GA: National Birth Defects Prevention Network. 2015.

Rashidi-Nezhad A, Parvaneh N, Farzanfar F, Azimi C, Harewood L, Akrami SM, et al. 2q34-qter duplication and 4q34. 2-qter deletion in a patient with developmental delay. Eur J Med Genet. 2012;55:203–10.

doi: 10.1016/j.ejmg.2012.01.012 pubmed: 22370062

Badv RS, Mahdiannasser M, Rasoulinezhad M, Habibi L, Rashidi-Nezhad A. CEP104 gene may involve in the pathogenesis of a new developmental disorder other than joubert syndrome. Mol Biol Rep. 2022;49:7231–7.

doi: 10.1007/s11033-022-07353-w pubmed: 35359234

Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Elsevier; 2020.

McGowan-Jordan J, Hastings RJ, Moore S ISCN 2020: an international system for human cytogenomic nomenclature (2020). (No Title). 2020.

Mahdiannasser M, Rashidi-Nezhad A, Badv RS, Akrami SM. Exploring the genetic etiology of drug-resistant epilepsy: incorporation of exome sequencing into practice. Acta Neurol Belgica. 2022;122:1457–68.

doi: 10.1007/s13760-022-02095-9

Li H, Durbin R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics. 2009;25:1754–60.

doi: 10.1093/bioinformatics/btp324 pubmed: 19451168 pmcid: 2705234

McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297–303.

doi: 10.1101/gr.107524.110 pubmed: 20644199 pmcid: 2928508

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–23.

doi: 10.1038/gim.2015.30 pubmed: 25741868 pmcid: 4544753

Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES, Getz G, et al. Integrative genomics viewer. Nat Biotechnol. 2011;29:24–6.

doi: 10.1038/nbt.1754 pubmed: 21221095 pmcid: 3346182

Moorthie S, Blencowe H, Darlison MW, Lawn J, Morris JK, Modell B, et al. Estimating the birth prevalence and pregnancy outcomes of congenital malformations worldwide. J community Genet. 2018;9:387–96.

doi: 10.1007/s12687-018-0384-2 pubmed: 30218347 pmcid: 6167261

Ely DM, Driscoll AK Infant mortality in the United States, 2017: data from the period linked birth/infant death file. 2019.

Staebler M, Donner C, Van Regemorter N, Duprez L, De Maertelaer V, Devreker F, et al. Should determination of the karyotype be systematic for all malformations detected by obstetrical ultrasound? Prenat Diagn. 2005;25:567–73.

doi: 10.1002/pd.1187 pubmed: 16032766

Vand-Rajabpour F, Mousavi F, Kariminejad R, Bagherizadeh I, Bahadory K, Giti S, et al. Evaluation and Report of Array-CGH Utility in prenatal and postnatal diagnosis and abortion products referred to a Diagnostic Laboratory in Tehran. Sarem J Med Res. 2021;6:135–41.

doi: 10.52547/sjrm.6.3.135

Evangelidou P, Sismani C, Ioannides M, Christodoulou C, Koumbaris G, Kallikas I, et al. Clinical application of whole-genome array CGH during prenatal diagnosis: Study of 25 selected pregnancies with abnormal ultrasound findings or apparently balanced structural aberrations. Mol Cytogenetics. 2010;3:1–10.

doi: 10.1186/1755-8166-3-24

Castells-Sarret N, Cueto-González AM, Borregan M, López-Grondona F, Miró R, Tizzano E, et al. Comparative genomic hybridisation as a first option in genetic diagnosis: 1000 cases and a cost–benefit analysis. An de Pediatría (Engl Ed). 2018;89:3–11.

Sagoo GS, Butterworth AS, Sanderson S, Shaw-Smith C, Higgins JP, Burton H. Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects. Genet Med. 2009;11:139–46.

doi: 10.1097/GIM.0b013e318194ee8f pubmed: 19367186

Najafi K, Gholami S, Moshtagh A, Bazrgar M, Sadatian N, Abbasi G, et al. Chromosomal aberrations in pregnancy and fetal loss: Insight on the effect of consanguinity, review of 1625 cases. Mol Genet Genom Med. 2019;7:e820.

doi: 10.1002/mgg3.820

Mohammadzadeh A, Akbaroghli S, Aghaei-Moghadam E, Mahdieh N, Badv RS, Jamali P, et al. Investigation of chromosomal abnormalities and microdeletion/microduplication (s) in fifty Iranian patients with multiple congenital anomalies. Cell J (Yakhteh). 2019;21:337.

pmcid: 6582423

Drury S, Williams H, Trump N, Boustred C, GOSGene, Lench N, et al. Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities. Prenat Diagn. 2015;35:1010–7.

doi: 10.1002/pd.4675 pubmed: 26275891

Ales M, Luca L, Marija V, Gorazd R, Karin W, Ana B, et al. Phenotype-driven gene target definition in clinical genome-wide sequencing data interpretation. Genet Med. 2016;18:1102.

doi: 10.1038/gim.2016.22

Retterer K, Juusola J, Cho MT, Vitazka P, Millan F, Gibellini F, et al. Clinical application of whole-exome sequencing across clinical indications. Genet Med. 2016;18:696–704.

doi: 10.1038/gim.2015.148 pubmed: 26633542

Nambot S, Thevenon J, Kuentz P, Duffourd Y, Tisserant E, Bruel A-L, et al. Clinical whole-exome sequencing for the diagnosis of rare disorders with congenital anomalies and/or intellectual disability: substantial interest of prospective annual reanalysis. Genet Med. 2018;20:645–54.

doi: 10.1038/gim.2017.162 pubmed: 29095811

Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA. 2014;312:1870–9.

doi: 10.1001/jama.2014.14601 pubmed: 25326635 pmcid: 4326249

Najafi K, Mehrjoo Z, Ardalani F, Ghaderi-Sohi S, Kariminejad A, Kariminejad R, et al. Identifying the causes of recurrent pregnancy loss in consanguineous couples using whole exome sequencing on the products of miscarriage with no chromosomal abnormalities. Sci Rep. 2021;11:1–12.

doi: 10.1038/s41598-021-86309-9

Stark Z, Schofield D, Alam K, Wilson W, Mupfeki N, Macciocca I, et al. Prospective comparison of the cost-effectiveness of clinical whole-exome sequencing with that of usual care overwhelmingly supports early use and reimbursement. Genet Med. 2017;19:867–74.

doi: 10.1038/gim.2016.221 pubmed: 28125081

Vissers LE, Van Nimwegen KJ, Schieving JH, Kamsteeg E-J, Kleefstra T, Yntema HG, et al. A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology. Genet Med. 2017;19:1055–63.

doi: 10.1038/gim.2017.1 pubmed: 28333917 pmcid: 5589982

Jegathisawaran J, Tsiplova K, Ungar WJ A microcosting and cost-consequence analysis of genomic testing strategies (including trios) in autism spectrum disorder: an update. The Hospital for Sick Children: Technology Assessment at SickKids. 2019.