Volume 25, Issue 6 (11-2021)                   IBJ 2021, 25(6): 441-446 | Back to browse issues page

PMID: 34641644


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Abstract:  
Background: Premature ovarian failure is a heterogeneous disorder, leading to early menopause. Several genes have been identified as the cause of non-syndromic premature ovarian failure (POF). Our aim was to explore the genetic defects in Iranian patients with POF. Methods: We studied a family with three females exhibiting non-syndromic POF. WES was performed for one of the affected individuals after ruling out the presence of CGG repeat expansion at fragile X mental retardation 1 gene in the family. Sanger sequencing was used to confirm the candidate sequence variants in the proband, and screening of the detected mutation was performed for the other affected and unaffected members of the family. Results: A homozygous frameshift mutation, c.349delC, was identified in ficolin-3 (FCN3) gene in the proband and two other patients. The parents and two healthy brothers were heterozygous for the mutation, and an unaffected sister was homozygous for wild type. Conclusion: This is the first report of a mutation in FCN3 gene in a family with POF. Our findings can lead to the enhancement of genetic databases of patients with POF, specifically for families with high-risk background.

References
1. Torrealday S, Kodaman P, Pal L. Premature Ovarian Insufficiency-an update on recent advances in understanding and management. F1000Research 2017; 6: 2069. [DOI:10.12688/f1000research.11948.1]
2. Simpson JL, Rajkovic A. Ovarian differentiation and gonadal failure. American journal of medical genetics 1999; 89(4): 186-200. https://doi.org/10.1002/(SICI)1096-8628(19991229)89:4<186::AID-AJMG3>3.0.CO;2-5 [DOI:10.1002/(SICI)1096-8628(19991229)89:43.0.CO;2-5]
3. Fortuño C, Labarta E. Genetics of primary ovarian insufficiency: a review. Journal of assisted reproduction and genetics 2014; 31(12): 1573-1585. [DOI:10.1007/s10815-014-0342-9]
4. Aittomäki K, Lucena JD, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila E-M, Lehväslaiho H, Engel AR. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 1995; 82(6): 959-968. [DOI:10.1016/0092-8674(95)90275-9]
5. Latronico AC, Anasti J, Arnhold IJ, Rapaport R, Mendonca BB, Bloise W, Castro M, Tsigos C, Chrousos GP. Testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the luteinizing hormone-receptor gene. New England journal of medicine 1996; 334(8): 507-512. [DOI:10.1056/NEJM199602223340805]
6. Chapman C, Cree L, Shelling AN. The genetics of premature ovarian failure: current perspectives. International journal of women's health 2015; 7: 799. [DOI:10.2147/IJWH.S64024]
7. De Vries L, Behar DM, Smirin-Yosef P, Lagovsky I, Tzur S, Basel-Vanagaite L. Exome sequencing reveals SYCE1 mutation associated with autosomal recessive primary ovarian insufficiency. The journal of clinical endocrinology and metabolism 2014; 99(10): E2129-E2132. [DOI:10.1210/jc.2014-1268]
8. Caburet S, Arboleda VA, Llano E, Overbeek PA, Barbero JL, Oka K, Harrison W, Vaiman D, Ben-Neriah Z, García-Tuñón I. Mutant cohesin in premature ovarian failure. The New England journal of medicine 2014; 370(10): 943-949. [DOI:10.1056/NEJMoa1309635]
9. Fonseca DJ, Patiño LC, Suárez YC, de Jesús Rodríguez A, Mateus HE, Jiménez KM, Ortega-Recalde O, Díaz-Yamal I, Laissue P. Next generation sequencing in women affected by nonsyndromic premature ovarian failure displays new potential causative genes and mutations. Fertility and sterility 2015; 104(1): 154-162. e152. [DOI:10.1016/j.fertnstert.2015.04.016]
10. Baronchelli S, Villa N, Redaelli S, Lissoni S, Saccheri F, Panzeri E, Conconi D, Bentivegna A, Crosti F, Sala E. Investigating the role of X chromosome breakpoints in premature ovarian failure. Molecular cytogenetics 2012; 5(1): 32. [DOI:10.1186/1755-8166-5-32]
11. Akrami SM, Montazeri V, Shomali SR, Heshmat R, Larijani B. Is there a significant trend in prevalence of consanguineous marriage in Tehran? A review of three generations. Journal of genetic counseling 2009; 18(1): 82. [DOI:10.1007/s10897-008-9191-y]
12. Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 2010; 26(5): 589-595. [DOI:10.1093/bioinformatics/btp698]
13. Meyer LR, Zweig AS, Hinrichs AS, Karolchik D, Kuhn RM, Wong M, Sloan CA, Rosenbloom KR, Roe G, Rhead B. The UCSC Genome Browser database: extensions and updates 2013. Nucleic acids research 2012; 41(D1): D64-D69. [DOI:10.1093/nar/gks1048]
14. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome research 2010; 20(9): 1297-1303 [DOI:10.1101/gr.107524.110]
15. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R. The sequence alignment/map format and SAMtools. Bioinformatics 2009; 25(16): 2078-2079. [DOI:10.1093/bioinformatics/btp352]
16. Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Hoover J. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic acids research 2015; 44(D1): D862-D868. [DOI:10.1093/nar/gkv1222]
17. Hamosh A, Scott AF, Amberger JS, Bocchini CA, McKusick VA. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic acids research 2005; 33(suppl_1): D514-D517. [DOI:10.1093/nar/gki033]
18. Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, Klemm A, Flicek P, Manolio T, Hindorff L. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic acids research 2013; 42(D1): D1001-D1006. [DOI:10.1093/nar/gkt1229]
19. Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, Abeysinghe S, Krawczak M, Cooper DN. Human gene mutation database (HGMD®): 2003 update. Human mutation 2003; 21(6): 577-581. [DOI:10.1002/humu.10212]
20. Mottaz A, David FP, Veuthey A-L, Yip YL. Easy retrieval of single amino-acid polymorphisms and phenotype information using SwissVar. Bioinformatics 2010; 26(6): 851-852. [DOI:10.1093/bioinformatics/btq028]
21. Michalski M, Szala A, Swierzko AS, Lukasiewicz J, Maciejewska A, Kilpatrick DC, Matsushita M, Domzalska-Popadiuk I, Borkowska-Klos M, Sokolowska A. H-ficolin (ficolin-3) concentrations and FCN3 gene polymorphism in neonates. Immunobiology 2012; 217(7): 730-737. [DOI:10.1016/j.imbio.2011.12.004]
22. Hummelshoj T, Fog LM, Madsen HO, Sim RB, Garred P. Comparative study of the human ficolins reveals unique features of Ficolin-3 (Hakata antigen). Molecular Immunology 2008; 45(6): 1623-1632. [DOI:10.1016/j.molimm.2007.10.006]
23. Ohashi T, Erickson HP. The disulfide bonding pattern in ficolin multimers. Journal of biological chemistry 2004; 279(8): 6534-6539. [DOI:10.1074/jbc.M310555200]
24. Kuraya M, Matsushita M, Endo Y, Thiel S, Fujita T. Expression of H‐ficolin/Hakata antigen, mannose‐ binding lectin‐associated serine protease (MASP)‐1 and MASP‐3 by human glioma cell line T98G. International immunology 2003; 15(1): 109-117. [DOI:10.1093/intimm/dxg008]
25. Szala A, Sawicki S, Swierzko AS, Szemraj J, Sniadecki M, Michalski M, Kaluzynski A, Lukasiewicz J, Maciejewska A, Wydra D. Ficolin-2 and ficolin-3 in women with malignant and benign ovarian tumours. Cancer Immunology, Immunotherapy 2013; 62(8): 1411-1419. [DOI:10.1007/s00262-013-1445-3]
26. Munthe-Fog L, Hummelshøj T, Ma YJ, Hansen BE, Koch C, Madsen HO, Skjødt K, Garred P. Characterization of a polymorphism in the coding sequence of FCN3 resulting in a Ficolin-3 (Hakata antigen) deficiency state. Molecular immunology 2008; 45(9): 2660-2666. [DOI:10.1016/j.molimm.2007.12.012]
27. Munthe-Fog L, Hummelshøj T, Honoré C, Madsen HO, Permin H, Garred P. Immunodeficiency associated with FCN3 mutation and ficolin-3 deficiency. The New England journal of medicine 2009, 360(25):2637-2644. [DOI:10.1056/NEJMoa0900381]
28. Schlapbach LJ, Thiel S, Kessler U, Ammann RA, Aebi C, Jensenius JC. Congenital H-ficolin deficiency in premature infants with severe necrotising enterocolitis. An international journal of gastroenterology and hepatology 2011; 60(10): 1438-1439. [DOI:10.1136/gut.2010.226027]
29. Michalski M, Świerzko AS, Pągowska-Klimek I, Niemir ZI, Mazerant K, Domżalska-Popadiuk I, Moll M, Cedzyński M. Primary Ficolin-3 deficiency-Is it associated with increased susceptibility to infections? Immunobiology 2015; 220(6): 711-713. [DOI:10.1016/j.imbio.2015.01.003]

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