Hongguo ZHANG, Ruixue WANG, Linlin LI, Haibo ZHU, Ruizhi LIU, Hao ZHANG

Translocation breakpoints of chromosome 3 in male carriers: a report of twelve cases and a review of the literature

Background/aim: This study aimed to explore the breakpoints in chromosome 3 translocation and the clinical features present in malecarriers to enable informed genetic counseling of these patients.Materials and methods: A total of 5235 men who were infertile or receiving counseling for infertility were recruited. Cytogeneticanalyses were performed using G-banding. A search for translocations on chromosome 3 involved in male infertility was performedusing PubMed, Google Scholar, and CNKI. The relationships of translocation breakpoints with male infertility and recurrent pregnancyloss were also analyzed.Results: Among the 82 patients with balanced reciprocal translocations among 5235 male patients, 12 patients were carriers ofchromosome 3 translocation: two presented with pregestational infertility, while 10 presented with gestational infertility. The breakpointat 3p13 was related to pregestational infertility, whereas those at 3p23, 3q10, 3q12, 3q21, 3q25, and 3q29 were related to gestationalinfertility. By an analysis combining data from the literature, 63 carriers of chromosome 3 translocation were reviewed and all breakpointsat chromosome 3 were correlated with gestational infertility.Conclusion: All breakpoints at chromosome 3 were correlated with gestational infertility. The breakpoints at 3q12 and 3q29 were themost common. Carriers of chromosome 3 translocation should thus be counseled on the need for other chromosomal breakpoints andpreimplantation genetic diagnosis or prenatal testing.

PDF

___

Song SH, Chiba K, Ramasamy R, Lamb DJ. Recent advances in the genetics of testicular failure. Asian J Androl 2016; 18: 350- 355.
Al-Turki HA. A 5-year analysis of semen parameters in Saudi Arabian men attending infertility clinics. J Int Med Res 2016; 44: 656-661.
Dul EC, Groen H, van Ravenswaaij-Arts CM, Dijkhuizen T, van Echten-Arends J, Land JA. The prevalence of chromosomal abnormalities in subgroups of infertile men. Hum Reprod 2012; 27: 36-43.
Gao M, Pang H, Zhao YH, Hua J, Tong D, Zhao H, Liu Y, Zhao Y, Zhang M, Yan XJ et al. Karyotype analysis in large sample cases from Shenyang Women’s and Children’s hospital: a study of 16,294 male infertility patients. Andrologia 2017; 49: 12649.
Hotaling J, Carrell DT. Clinical genetic testing for male factor infertility: current applications and future directions. Andrology 2014; 2: 339-350.
Pastuszek E, Kiewisz J, Kulwikowska PM, Lukaszuk M, Lukaszuk K. Sperm parameters and DNA fragmentation of balanced chromosomal rearrangements carriers. Folia Histochem Cytobiol 2015; 53: 314-321.
Suganya J, Kujur SB, Selvaraj K, Suruli MS, Haripriya G, Samuel CR. Chromosomal Abnormalities in Infertile Men from Southern India. J Clin Diagn Res 2015; 9: GC05-10.
Harton GL, Tempest HG. Chromosomal disorders and male infertility. Asian J Androl 2012; 14: 32-39.
Godo A, Blanco J, Vidal F, Anton E. Accumulation of numerical and structural chromosome imbalances in spermatozoa from reciprocal translocation carriers. Hum Reprod 2013; 28: 840- 849.
Zhang HG, Wang RX, Li LL, Sun WT, Zhang HY, Liu RZ. Male carriers of balanced reciprocal translocations in Northeast China: sperm count, reproductive performance, and genetic counseling. Genet Mol Res 2015; 14: 18792-18798.
Gada Saxena S, Desai K, Shewale L, Ranjan P, Saranath D. Chromosomal aberrations in 2000 couples of Indian ethnicity with reproductive failure. Reprod Biomed Online 2012; 25: 209-218.
Mierla D, Jardan D, Stoian V. Chromosomal abnormality in men with impaired spermatogenesis. Int J Fertil Steril 2014; 8: 35-42.
Tunç E, Tanrıverdi N, Demirhan O, Süleymanova D, Çetinel N. Chromosomal analyses of 1510 couples who have experienced recurrent spontaneous abortions. Reprod Biomed Online 2016; 32: 414-419.
Martini E, von Bergh AR, Coonen E, de Die-Smulders CE, Hopman AH, Ramaekers FC, Geraedts JP. Detection of structural abnormalities in spermatozoa of a translocation carrier t(3;11)(q27.3;q24.3) by triple FISH. Hum Genet 1998; 102: 157-165.
Martin RH. Sperm chromosome complements in a man heterozygous for a reciprocal translocation t(2;3)(q24;p26). Hum Reprod 1994; 9: 1512-1515.
Gross C, De Baere E, Lo A, Chang W, Messiaen L. Cloning and characterization of human WDR10, a novel gene located at 3q21 encoding a WD-repeat protein that is highly expressed in pituitary and testis. DNA Cell Biol 2001; 20: 41-52.
Shalata A, Ramirez MC, Desnick RJ, Priedigkeit N, Buettner C, Lindtner C, Mahroum M, Abdul-Ghani M, Dong F, Arar N et al. Morbid obesity resulting from inactivation of the ciliary protein CEP19 in humans and mice. Am J Hum Genet 2013; 93: 1061-1071.
Zhang HG, Liu XY, Hou Y, Chen S, Deng S, Liu RZ. Reproductive outcome of a case with familial balanced translocation t(3;6): implications for genetic counseling. Genet Mol Res 2015; 14: 2809-2815.
Pasquier L, Fradin M, Chérot E, Martin-Coignard D, Colin E, Journel H, Demurger F, Akloul L, Quélin C, Jauffret V et al. Karyotype is not dead (yet)! Eur J Med Genet 2016; 59: 11-15.
Poli MN, Miranda LA, Gil ED, Zanier GJ, Iriarte PF, Zanier JH, Coco R. Male cytogenetic evaluation prior to assisted reproduction procedures performed in Mar del Plata, Argentina. JBRA Assist Reprod 2016; 20: 62-65.
Stouffs K, Seneca S, Lissens W. Genetic causes of male infertility. Ann Endocrinol (Paris) 2014; 75: 109-111.
Zhang M, Fan HT, Zhang QS, Wang XY, Yang X, Tian WJ, Li RW. Genetic screening and evaluation for chromosomal abnormalities of infertile males in Jilin Province, China. Genet Mol Res 2015; 14: 16178-16184.
Li D, Zhang H, Wang R, Zhu H, Li L, Liu R. Chromosomal abnormalities in men with pregestational and gestational infertility in northeast China. J Assist Reprod Genet 2012; 29: 829-836.
Fryns JP, Van Buggenhout G. Structural chromosome rearrangements in couples with recurrent fetal wastage. Eur J Obstet Gynecol Reprod Biol 1998; 81: 171-176.
Kochhar PK, Ghosh P. Reproductive outcome of couples with recurrent miscarriage and balanced chromosomal abnormalities. J Obstet Gynaecol Res 2013; 39: 113-120.
Vozdova M, Oracova E, Kasikova K, Prinosilova P, Rybar R, Horinova V, Gaillyova R, Rubes J. Balanced chromosomal translocations in men: relationships among semen parameters, chromatin integrity, sperm meiotic segregation and aneuploidy. J Assist Reprod Genet 2013; 30: 391-405.
Li LL, Dong Y, Wang RX, An N, Yun X, Liu RZ. Sperm aneuploidy and implications for genetic counseling in a pedigree of three t(1;3) balanced translocation carriers. Genet Mol Res 2015; 14: 5003-5009.
Venkateshwari A, Srilekha A, Begum A, Sujatha M, Sunitha T, Nallari P, Jyothy A. De novo chromosomal translocation t(3;5) (q13;q35) in an infertile man. Andrologia 2011; 43: 428-430.
Mokánszki A, Ujfalusi A, Balogh E, Sümegi A, Antal-Szalmás P, Bazsáné ZK, Molnár Z, Varga A, Sápy T, Jakab A et al. Meiotic segregation study of a novel t(3;6)(q21;q23) in an infertile man using fluorescence in situ hybridization (FISH). Syst Biol Reprod Med 2012; 58: 160-164.
Dong Y, Du RC, Jiang YT, Wu J, Li LL, Liu RZ. Impact of chromosomal translocations on male infertility, semen quality, testicular volume and reproductive hormone levels. J Int Med Res 2012; 40: 2274-2283.
Gaboon NE, Mohamed AR, Elsayed SM, Zaki OK, Elsayed MA. Structural chromosomal abnormalities in couples with recurrent abortion in Egypt. Turk J Med Sci 2015; 45: 208-213.
Celep F, Karagüzel A, Ozeren M, Bozkaya H. The frequency of chromosomal abnormalities in patients with reproductive failure. Eur J Obstet Gynecol Reprod Biol 2006; 127: 106-109.
Dutta UR, Rajitha P, Pidugu VK, Dalal AB. Cytogenetic abnormalities in 1162 couples with recurrent miscarriages in southern region of India: report and review. J Assist Reprod Genet 2011; 28: 145-149.
Dul EC, van Echten-Arends J, Groen H, Dijkhuizen T, Land JA, van Ravenswaaij-Arts CM. Chromosomal abnormalities in azoospermic and non-azoospermic infertile men: numbers needed to be screened to prevent adverse pregnancy outcomes. Hum Reprod 2012; 27: 2850-2856.
Escudero T, Abdelhadi I, Sandalinas M, Munné S. Predictive value of sperm fluorescence in situ hybridization analysis on the outcome of preimplantation genetic diagnosis for translocations. Fertil Steril 2003; 79 (Suppl. 3): 1528-1534.
Perrin A, Caer E, Oliver-Bonet M, Navarro J, Benet J, Amice V, De Braekeleer M, Morel F. DNA fragmentation and meiotic segregation in sperm of carriers of a chromosomal structural abnormality. Fertil Steril 2009; 92: 583-589.
Oliver-Bonet M, Navarro J, Carrera M, Egozcue J, Benet J. Aneuploid and unbalanced sperm in two translocation carriers: evaluation of the genetic risk. Mol Hum Reprod 2002; 8: 958-963.
Haapaniemi Kouru K, Malmgren H, White I, Rodriguez Sanchez A, Syk Lundberg E. Meiotic segregation analyses of reciprocal translocations in spermatozoa and embryos: no support for predictive value regarding PGD outcome. Reprod Biomed Online 2017; 34: 645-652.
Rouen A, Carlier L, Heide S, Egloff M, Marzin P, Ader F, Schwartz M, Rogers E, Joyé N, Balet R et al. Potential selection of genetically balanced spermatozoa based on the hypoosmotic swelling test in chromosomal rearrangement carriers. Reprod Biomed Online 2017; 35: 372-378.
Matsuda T, Horii Y, Ogura K, Nonomura M, Okada K, Yoshida O. Chromosomal survey of 1001 subfertile males: incidence and clinical features of males with chromosomal anomalies. Hinyokika Kiyo 1992; 38: 803-809.
Zhang YP, Xu JZ, Yin M, Chen MF, Ren DL. Pregnancy outcomes of 194 couples with balanced translocations. Zhonghua Fu Chan Ke Za Zhi 2006; 41: 592-596.
Kyu Lim C, Hyun Jun J, Mi Min D, Lee HS, Young Kim J, Koong MK, Kang IS. Efficacy and clinical outcome of preimplantation genetic diagnosis using FISH for couples of reciprocal and Robertsonian translocations: the Korean experience. Prenat Diagn 2004; 24: 556-561.
Ko DS, Cho JW, Park SY, Kim JY, Koong MK, Song IO, Kang IS, Lim CK. Clinical outcomes of preimplantation genetic diagnosis (PGD) and analysis of meiotic segregation modes in reciprocal translocation carriers. Am J Med Genet A 2010; 152A: 1428-1433.
Castle D, Bernstein R. Cytogenetic analysis of 688 couples experiencing multiple spontaneous abortions. Am J Med Genet 1988; 29: 549-556.
Adamoli A, Bernardi F, Chiaffoni G, Fraccaro M, Giardino D, Romitti L, Simoni G. Reproductive failure and parental chromosome abnormalities. Hum Reprod 1986; 1: 99-102.
Ocak Z, Özlü T, Ozyurt O. Association of recurrent pregnancy loss with chromosomal abnormalities and hereditary thrombophilias. Afr Health Sci 2013; 13: 447-452.
Brandriff B, Gordon L, Ashworth LK, Littman V, Watchmaker G, Carrano AV. Cytogenetics of human sperm: meiotic segregation in two translocation carriers. Am J Hum Genet 1986; 38: 197-208.
Antonelli A, Gandini L, Petrinelli P, Marcucci L, Elli R, Lombardo F, Dondero F, Lenzi A. Chromosomal alterations and male infertility. J Endocrinol Invest 2000; 23: 677-683.
Goddijn M, Joosten JH, Knegt AC, van der Veen F, Franssen MT, Bonsel GJ, Leschot NJ. Clinical relevance of diagnosing structural chromosome abnormalities in couples with repeated miscarriage. Hum Reprod 2004; 19: 1013-1017.
Estop AM, Van Kirk V, Cieply K. Segregation analysis of four translocations, t(2;18), t(3;15), t(5;7), and t(10;12), by sperm chromosome studies and a review of the literature. Cytogenet Cell Genet 1995; 70: 80-87.
Gekas J, Thepot F, Turleau C, Siffroi JP, Dadoune JP, Briault S, Rio M, Bourouillou G, Carré-Pigeon F, Wasels R et al. Chromosomal factors of infertility in candidate couples for ICSI: an equal risk of constitutional aberrations in women and men. Hum Reprod 2001; 16: 82-90.
Gianaroli L, Magli MC, Ferraretti AP, Munné S, Balicchia B, Escudero T, Crippa A. Possible interchromosomal effect in embryos generated by gametes from translocation carriers. Hum Reprod 2002; 17: 3201-3207.
Iyer P, Wani L, Joshi S, Lakshmi J, Dalvi R, Chavan D, Das BR, Mandava S. Cytogenetic investigations in couples with repeated miscarriages and malformed children: report of a novel insertion. Reprod Biomed Online 2007; 14: 314-321.
Sugiura-Ogasawara M, Aoki K, Fujii T, Fujita T, Kawaguchi R, Maruyama T, Ozawa N, Sugi T, Takeshita T, Saito S. Subsequent pregnancy outcomes in recurrent miscarriage patients with a paternal or maternal carrier of a structural chromosome rearrangement. J Hum Genet 2008; 53: 622-628.
Portnoï MF, Joye N, van den Akker J, Morlier G, Taillemite JL. Karyotypes of 1142 couples with recurrent abortion. Obstet Gynecol 1988; 72: 31-34.
Machev N, Gosset P, Warter S, Treger M, Schillinger M, Viville S. Fluorescence in situ hybridization sperm analysis of six translocation carriers provides evidence of an interchromosomal effect. Fertil Steril 2005; 84: 365-373.
Meza-Espinoza JP, Anguiano LO, Rivera H. Chromosomal abnormalities in couples with reproductive disorders. Gynecol Obstet Invest 2008; 66: 237-240.
Pundir J, Magdalani L, El-Toukhy T. Outcome of preimplantation genetic diagnosis using FISH analysis for recurrent miscarriage in low-risk reciprocal translocation carriers. Eur J Obstet Gynecol Reprod Biol 2016; 203: 214-219.
Vegetti W, Van Assche E, Frias A, Verheyen G, Bianchi MM, Bonduelle M, Liebaers I, Van Steirteghem A. Correlation between semen parameters and sperm aneuploidy rates investigated by fluorescence in-situ hybridization in infertile men. Hum Reprod 2000; 15: 351-365.
Peschka B, Leygraaf J, Van der Ven K, Montag M, Schartmann B, Schubert R, van der Ven H, Schwanitz G. Type and frequency of chromosome aberrations in 781 couples undergoing intracytoplasmic sperm injection. Hum Reprod 1999; 14: 2257-2263.
Martin RH, Hultén M. Chromosome complements in 695 sperm from three men heterozygous for reciprocal translocations, and a review of the literature. Hereditas 1993; 118: 165-175.
Jenderny J. Sperm chromosome analysis of two males heterozygous for a t(2;17)(q35;p13) and t(3;8)(p13;p21) reciprocal translocation. Hum Genet 1992; 90: 171-173.