Association of Pericentric Inv(12)(p11.2q14) with Infertility and Recurrent Miscarriages: Case Report and Literature Review

Abstract

Infertility, reported in 15% of the couples who want to have children, is an important worldwide health problem. Recurrent miscarriage, observed in 15–25% of pregnancies, is another important health issue affecting millions of couples in the world. Despite many genetic factors have been associated with infertility or recurrent miscarriages especially in recent years, the genetic and epigenetic factors underlying these problems are mostly unknown. Most of the pericentric inversions do not affect phenotypes of the individuals carrying balanced rearrangements. However, the pericentric inversions may cause chromosomally unbalanced sperm/ovum during the meiotic crossover leading to infertility or recurrent miscarriages. In this case report, we report a familial pericentric inv(12)(p11.2q14) in eight individuals with infertility or recurrent miscarriages in three different families.

Keywords

• Infertility,recurrent miscarriages,pericentric inversion,inv(12)(p11.2q14)

Perisentrik inv(12)(p11.2q14)’nin İnfertilite ve Tekrarlayan Düşüklerle İlişkisi: Vaka Örneği ve Literatür Taraması

Abstract

Çocuk sahibi olmak isteyen çiftlerin %15'inde görülen infertilite, tüm dünyada önemli bir sağlık sorunudur. Gebeliklerin %15-25'inde gözlenen tekrarlayan düşükler, dünya genelinde milyonlarca çifti etkileyen bir diğer önemli sorundur. Özellikle son yıllarda infertilite ya da tekrarlayan düşüklüklerle pek çok genetik faktör ilişkilendirilmiş olsa da, bu sorunların altında yatan genetik ve epigenetik faktörlerin çok büyük kısmı henüz bilinmemektedir. Perisentrik inversiyonların çoğu, taşıyıcı bireylerin fenotipini etkilemez. Bununla birlikte mayoz bölünmenin krosing over aşamasında hatalara neden olabilen perisentrik inversiyonlar infertiliteye veya tekrarlayan düşüklere yol açabilir. Bu olgu sunumu çalışmasında, üç farklı aileden sekiz bireyde tespit ettiğimiz pericentric inv(12)(p11.2q14)’ün infertilite ve tekrarlayan düşüklerle ilişkisi üzerinde durulmuştur.

Keywords

• İnfertilite,tekrarlayan düşükler,perisentrik inversiyon,inv(12)(p11.2q14)

References

1. Kamel RM. Management of the infertile couple: an evidence-based protocol. Reprod Biol Endocrinol. 2010;8:21.
2. El Hachem H, Crepaux V, May-Panloup P, Descamps P, Legendre G, Bouet P-E. Recurrent pregnancy loss: current perspectives. Int J Womens Health. 2017;9:331-45.
3. Hyde KJ, Schust DJ. Genetic considerations in recurrent pregnancy loss. Cold Spring Harb Perspect Med. 2015;5(3):a023119.
4. Sturtevant AH. A case of rearrangement of genes in Drosophila. Proc Natl Acad Sci U S A. 1921;7(8):235-7.
5. Tayebi N, Khodaei H. A rare case of pericentric inversion, Inv (21) (p12;q22) in repeated pregnancy loss: A case report. Oman Med J. 2011;26(6):441-3.
6. Naseeb S, Carter Z, Minnis D, Donaldson I, Zeef L, Delneri D. Widespread impact of chromosomal inversions on gene xxpression uncovers robustness via phenotypic buffering. Mol Biol Evol. 2016;33(7):1679-96.
7. Luo Y, Xu C, Sun Y, Wang L, Chen S, Jin F. Different segregation patterns in five carriers due to a pericentric inversion of chromosome 1. Syst Biol Reprod Med. 2014;60(6):367-72.
8. Utami KH, Hillmer AM, Aksoy I, Chew EG, Teo AS, Zhang Z, et al. Detection of chromosomal breakpoints in patients with developmental delay and speech disorders. PLoS One. 2014;9(6):e90852.

9. Anton E, Vidal F, Egozcue J, Blanco J. Genetic reproductive risk in inversion carriers. Fertil Steril. 2006;85(3):661-6.
10. Puig M, Casillas S, Villatoro S, Cáceres M. Human inversions and their functional consequences. Brief Funct Genomics. 2015;14(5):369-79.
11. Aristidou C, Koufaris C, Theodosiou A, Bak M, Mehrjouy MM, Behjati F, et al. Accurate breakpoint mapping in apparently balanced translocation families with discordant phenotypes using whole genome mate-pair sequencing. PLoS One. 2017;12(1):e0169935.
12. Prieto F, Badia L, Asensi F, Moya A, Figuera MJ. Pericentric inversions of chromosome 12 in two families. Hum Genet. 1981;57(2):131-3.
13. Varela M, Wang N, Cerrillo M. Prenatal diagnosis of a 46,XX,inv(12)pat/47,XX,i(Xq),inv(12)pat. Hum Genet. 1987;75(1):93-4.
14. Haagerup A, Hertz JM. Pericentric inversion of chromosome 12; a three family study. Hum Genet. 1992;89(3):292-4.
15. Singh RP. Klinefelter's syndrome with a 47,XXY, inv (12) (q15q24) karyotype. Clin Genet. 1981;19(3):188-90.
16. Silahtaroglu AN, Hacihanefioglu S, Güven GS, Cenani A, Wirth J, Tommerup N, et al. Not para-, not peri-, but centric inversion of chromosome 12. J Med Genet. 1998;35(8):682-4.
17. Voiculescu I, Barbi G, Wolff G, Steinbach P, Back E, Schempp W. Familial pericentric inversion of chromosome 12. Hum Genet. 1986;72(4):320-2.
18. Kim HJ, Levy J, Roguero W, Iu B, Wallach RC. Prenatal detection of pericentric inversion of chromosome 12. Diagn Gynecol Obstet. 1980;2(3):231-4.
19. Poulsen H, Mikkelsen M, Holmgren G. Peri- and paracentric inversions in chromosome 12: prenatal diagnosis and family study. Prenat Diagn. 1981;1(1):35-42.
20. Kleczkowska A, Fryns JP, Van den Berghe H. Pericentric inversions in man: personal experience and review of the literature. Hum Genet. 1987;75(4):333-8.
21. Uehara S, Tanigawara S, Takeyama Y, Okamura K, Yajima A. A family with pericentric inversion of chromosome 12. Jpn J Hum Genet. 1994;39(1):201-4.
22. Ghorbel M, Baklouti-Gargouri S, ElGhazel H, Zribi N, Ben Abdallah F, Cherif M, et al. Pericentric inversion of chromosom 12 [Inv (12) (p12q12)] associated with idiopathic azoospermia in one infertile Tunisian man. Biochem Biophys Res Commun. 2013;432(3):472-4.