Volume 21, Issue 8 (August 2023)                   IJRM 2023, 21(8): 667-672 | Back to browse issues page

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Nikuei P, khashavi Z, Farazi Fard M A, Tabasi S, Zeidi A, Pourkashan P, et al . Prenatal diagnosis of Sex determining region Y -box transcription factor 2 anophthalmia syndrome caused by germline mosaicism using next-generation sequencing: A case report. IJRM 2023; 21 (8) :667-672
URL: http://ijrm.ir/article-1-2750-en.html
Prenatal diagnosis of Sex determining region Y -box transcription factor 2 anophthalmia syndrome caused by germline mosaicism using next-generation sequencing: A case report
Pooneh Nikuei1 , Zahra Khashavi2 , Mohammad Ali Farazi Fard3 , Shahrzad Tabasi4 , Ari Zeidi5 , Parnian Pourkashan6 , Zahra Tabatabae3 , Ebrahim Eftekhar7 , Mozhgan Saberi8 , Frouzandeh Mahjoubi * 9
1- Hormozgan State of Welfare Organization, Bandar Abbas, Iran.
2- Gambron Royan Infertility Center, Bandar Abbas, Iran.
3- Persian Bayan Gene Research and Training Center, Shiraz, Iran.
4- Department of Clinical Pharmacy, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
5- New York University, NY, USA.
6- Iran University of Medical Sciences, Tehran, Iran.
7- Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
8- Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
9- Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. , frouz@nigeb.ac.ir
Abstract:   (331 Views)
Background: Sex determining region Y box transcription factor 2 (SOX2) mutations lead to bilateral anophthalmia with autosomal dominant human inheritance. SOX2 mutations could result in severe ocular phenotypes usually associated with variable systemic defects. Most patients described with SOX2 anophthalmia syndrome possessed de novo mutations in this gene.
Case Presentation: In this case report, we describe 2 brothers with mental retardation and bilateral anophthalmia caused due to SOX2 germline mosaicism in unaffected parents. Next-generation DNA sequencing was carried out to determine the family’s possible cause of genetic mutation. Sanger sequencing was performed on the patients and their parents. Prenatal diagnosis was done in both pregnancies of the older brother’s wife via chorionic villus sampling. A novel heterozygous pathogenic frameshift deletion variant (exon1:c.58_80del:p.G20fs) was identified in the SOX2 gene, which was confirmed by Sanger sequencing in both affected brothers and did not exist in healthy parents, indicating germline mosaicism.
Conclusion: Most SOX2 mutations known look to arise de novo in probands and are diagnosed through anophthalmia or microphthalmia. Prenatal diagnosis should be offered to healthy parents with a child with SOX2 mutation every pregnancy.
Keywords: Anophthalmos, SOX2 anophthalmia syndrome, Mosaicism.
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Type of Study: Original Article | Subject: Reproductive Genetics
References
1. Campbell IM, Yuan BO, Robberecht C, Pfundt R, Szafranski P, McEntagart ME, et al. Parental somatic mosaicism is underrecognized and influences recurrence risk of genomic disorders. Am J Hum Genet 2014; 95: 173-182. [DOI:10.1016/j.ajhg.2014.07.003] [PMID] [PMCID]
2. Dai C, Cheng D, Li W, Zeng S, Lu G, Zhang Q. Identification of paternal germline mosaicism by MicroSeq and targeted next‐generation sequencing. Mol Genet Genomic Med 2020; 8: e1394. [DOI:10.1002/mgg3.1394] [PMID] [PMCID]
3. Biesecker LG, Spinner NB. A genomic view of mosaicism and human disease. Nat Rev Genet 2013; 14: 307-320. [DOI:10.1038/nrg3424] [PMID]
4. Samuels ME, Friedman JM. Genetic mosaics and the germ line lineage. Genes 2015; 6: 216-237. [DOI:10.3390/genes6020216] [PMID] [PMCID]
5. Mohiuddin M, Kooy RF, Pearson CE. De novo mutations, genetic mosaicism and human disease. Front Genet 2022; 13: 983668. [DOI:10.3389/fgene.2022.983668] [PMID] [PMCID]
6. Amlie‐Wolf L, Bardakjian T, Kopinsky SM, Reis LM, Semina EV, Schneider A. Review of 37 patients with SOX2 pathogenic variants collected by the Anophthalmia/Microphthalmia Clinical Registry and DNA research study. Am J Med Genet A 2022; 188: 187-198. [DOI:10.1002/ajmg.a.62518] [PMID] [PMCID]
7. Watkins KE, Coullon GSL, Bridge H. Language and nonverbal auditory processing in the occipital cortex of individuals who are congenitally blind due to anophthalmia. Neuropsychologia 2022; 173: 108304. [DOI:10.1016/j.neuropsychologia.2022.108304] [PMID]
8. Chassaing N, Gilbert‐Dussardier B, Nicot F, Fermeaux V, Encha‐Razavi F, Fiorenza M, et al. Germinal mosaicism and familial recurrence of a SOX2 mutation with highly variable phenotypic expression extending from AEG syndrome to absence of ocular involvement. Am J Med Genet A 2007; 143: 289-291. [DOI:10.1002/ajmg.a.31524] [PMID]
9. Williamson KA, Hever AM, Rainger J, Rogers RC, Magee A, Fiedler Z, et al. Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome. Hum Mol Genet 2006; 15: 1413-1422. https://doi.org/10.1093/hmg/ddl127 [DOI:10.1093/hmg/ddl064] [PMID]
10. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25: 1754-1760. [DOI:10.1093/bioinformatics/btp324] [PMID] [PMCID]
11. 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: 1297-1303. [DOI:10.1101/gr.107524.110] [PMID] [PMCID]
12. Wang K, Li M, Hakonarson H. ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010; 38: e164. [DOI:10.1093/nar/gkq603] [PMID] [PMCID]
13. Dash S, Brastrom LK, Patel SD, Scott CA, Slusarski DC, Lachke SA. The master transcription factor SOX2, mutated in anophthalmia/microphthalmia, is post-transcriptionally regulated by the conserved RNA-binding protein RBM24 in vertebrate eye development. Hum Mol Genet 2020; 29: 591-604. [DOI:10.1093/hmg/ddz278] [PMID] [PMCID]
14. Fantes J, Ragge NK, Lynch S-A, McGill NI, Collin JRO, Howard-Peebles PN, et al. Mutations in SOX2 cause anophthalmia. Nat Genet 2003; 33: 461-463. [DOI:10.1038/ng1120] [PMID]
15. Pasmant E, Pacot L. Should we genotype the sperm of fathers from patients with 'de novo' mutations? Eur J Endocrinol 2020; 182: C1-C3. [DOI:10.1530/EJE-19-0759] [PMID]
16. Zenteno JC, Perez‐Cano HJ, Aguinaga M. Anophthalmia‐esophageal atresia syndrome caused by an SOX2 gene deletion in monozygotic twin brothers with markedly discordant phenotypes. Am J Med Genet A 2006; 140: 1899-1903. [DOI:10.1002/ajmg.a.31384] [PMID]
17. Schneider A, Bardakjian TM, Zhou J, Hughes N, Keep R, Dorsainville D, et al. Familial recurrence of SOX2 anophthalmia syndrome: Phenotypically normal mother with two affected daughters. Am J Med Genet A 2008; 146: 2794-2798. [DOI:10.1002/ajmg.a.32384] [PMID] [PMCID]
18. Morrison D, FitzPatrick D, Hanson I, Williamson K, Van Heyningen V, Fleck B, et al. National study of microphthalmia, anophthalmia, and coloboma (MAC) in Scotland: Investigation of genetic aetiology. J Med Genet 2002; 39: 16-22. [DOI:10.1136/jmg.39.1.16] [PMID] [PMCID]
19. Zlotogora J. Germ line mosaicism. Hum Genet 1998; 102: 381-386. [DOI:10.1007/s004390050708] [PMID]
20. Mohrenweiser H, Zingg B. Mosaicism: The embryo as a target for induction of mutations leading to cancer and genetic disease. Environ Mol Mutagen 1995; 25 (Suppl.): 21-29. [DOI:10.1002/em.2850250606] [PMID]
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