Cytogenetic Evaluation and Clinical Correlation: A Retrospective Analysis of East Indian Patients with Diverse Amenorrhea Profiles

Patel, Sunny; Banerjee, Birendranath

doi:10.18502/jri.v25i4.18129

Cytogenetic Evaluation and Clinical Correlation: A Retrospective Analysis of East Indian Patients with Diverse Amenorrhea Profiles

Authors

Sunny Patel ¹

Birendranath Banerjee ²

¹ Molecular Stress and Stem Cell Biology Group, School of Biotechnology, Kalinga Institute of Industrial Technology, Odisha, India; inDNA Center for Research and Innovation in Molecular Diagnostics, inDNA Life Sciences Pvt. Ltd., Od

² inDNA Center for Research and Innovation in Molecular Diagnostics, inDNA Life Sciences Pvt. Ltd., Odisha, India; JBS Haldane Centre for Molecular Medicine, Silicon University, Odisha, India

10.18502/jri.v25i4.18129

Abstract

Background: Amenorrhea is defined as the absence of menstruation in women at reproductive age, caused by imbalanced hormonal interactions. The genes located on X chromosome are linked to the physiology of menstruation and reproduction, and early detection of major chromosomal conditions can be facilitated through cytogenetic testing. This study aimed to determine the frequency and spectrum of chromosomal anomalies in amenorrhea patients from Eastern India and correlate clinical features with cytogenetic findings. Methods: From September 2022 to September 2024, 231 women with confirmed amenorrhea were included in a study conducted at inDNA Life Sciences Private Limited, India. Clinical features of women with a history of amenorrhea were recorded and cytogenetic investigation was carried out for all women. Results: Study revealed that 20.35% of amenorrhea cases exhibited chromosomal anomalies. Among them, 38.30% were classified as numerical anomalies, 25.53% as sex reversal, 19.15% as structural anomalies, and 17.02% as mosaic karyotypes, with X-monosomy identified as the most prevalent anomaly. Conclusion: The findings emphasizes the importance of karyotyping in diagnosis, highlighting its role in early detection and management of female infertility. Karyotyping has a resolution limit of 4-5 Mb, which disables identification of submicroscopic chromosomal abnormalities. In contrast, chromosomal microarray (CMA) analysis can examine the entire genome at higher resolutions, allowing for the identification of genetic abnormalities that may not be detected by karyotyping. While CMA was excluded from this investigation, it could serve as a valuable technique for future research aimed at identifying submicroscopic chromosomal abnormalities in cytogenetically normal women with amenorrhea.

Keywords

Amenorrhea

Chromosomal anomalies

Conventional cytogenetic analysis

Isochromosome

Ivalla AP. Prospective study of primary amenorrhoea and its management in a rural tertiary centre. Int J Reprod Contracept Obstet Gynecol. 2019;8(9):3442.

Bai BF, Padhiar C, Rao SP, Sujithra A, Banu SE, Santhosh A. Clinical investigation of the primary and secondary amenorrhea by cytogenetic analysis. J Appl Biol Biotechnol. 2022;10(6):81-6.

Mohajertehran F, Ghodsi K, Hafizi L, Rezaee A. Frequency and the type of chromosomal abnormalities in patients with primary amenorrhea in northeast of Iran. Iran J Basic Med Sci. 2013;16(4):643-7.

He Y, Zheng D, Shang W, Wang X, Zhao S, Wei Z, et al. Prevalence of oligomenorrhea among women of childbearing age in China: a large community-based study. Womens Health. 2020;16: 1745506520928617.

Susheela BR. Etiological factors of primary amenorrhoea: a prospective study. Int J Clin Obstet Gynaecol. 2019;3(4):228-30.

Malla TM, Dar FA, Pandith AA, Zargar MH. Frequency and pattern of cytogenetic alterations in primary amenorrhea cases of Kashmir, North India. Egyptian J Med Hum Genet. 2016;17(1):25-31.

Motamedirad N, Hosseini S, Ebrahimzadeh-Vesal R, Tootian S, Abbaszadegan MR. Investigation of the frequency and type of chromosomal abnormalities in women patients with amenorrhea. Rep Biochem Mol Biol. 2022;11(3):450-6.

Pal AK, Ambulkar PS, Sontakke BR, Talhar SS, Bokariya P, Gujar VK. A study on chromosomal analysis of patients with primary amenorrhea. J Hum Reprod Sci. 2019;12(1):29-34.

Migeon BR, Lee CH, Chowdhury AK, Carpenter H. Species differences in TSIX/Tsix reveal the roles of these genes in X-chromosome inactivation. Am J Hum Genet. 2002;71(2):286-93.

Pritti K, Mishra V, Patel H, Patel K, Aggarwal R, Choudhary S. Cytogenetic evaluation of primary amenorrhea: a study of 100 cases at tertiary centre. Egypt J Med Hum Genet. 2022;23(1):151.

Vijay C, Tilak P, Amudha S, Margaret M, Raina P. Cytogenetic abnormalities identified in cases of amenorrhea. J South Asian Federation Obstet Gynaecology. 2024;16(1):6-11.

Soltani N, Mirzaei F, Ayatollahi H. Cytogenetic study of patients with primary amenorrhea in the northeast of Iran. Iran J Pathol. 2020;16(1):57-61.

Jyothy A, Kumar KS, Swarna M, Sekhar MR, Devi BU, Reddy PP. Cytogenetic investigations in 1843 referral cases of disordered sexual development from andhra pradesh, India. Int J Hum Genet. 2002;2(1):55-9.

Wong MSF, Lam STS. Cytogenetic analysis of patients with primary and secondary amenorrhoea in Hong Kong: retrospective study. Hong Kong Med J. 2005;11(4):267-72.

Rajangam S, Nanjappa L. Cytogenetic studies in amenorrhea. Saudi Med J. 2007;28(2):187-92.

Ghodsi K, Tehran FM, Hafizi L. Chromosomal abnormalities showed on amenorrhea patients. J Med Genet. 2011;48:S86-S86.

Dutta UR, Ponnala R, Pidugu VK, Dalal AB. Chromosomal abnormalities in amenorrhea: a retrospective study and review of 637 patients in South India. Arch Iran Med. 2013;16(5):267-70.

Kumar S, Devi R. Clinical spectrum and cytogenetic characterization of patients with turner syndrome-twin case report. J Curr Res Sci Med. 2022;8(2):192-6.

Butnariu L, Covic M, Ivanov I, Bujoran C, Gramescu M, Gorduza EV. Clinical and cytogenetic correlation in primary and secondary amenorrhea: retrospective study on 531 patients. Revista Română de Medicină de Laborator. 2011;19(2/4).

Rajitha V, Rekha G, Nathan SS. A study of cytogenetic pattern in amenorrhea. Int J Anatomy Radiol Surg. 2017;6(3):10-15.

Samarakoon L, Sirisena ND, Wettasinghe KT, Kariyawasam KWJC, Jayasekara RW, Dissanayake VHW. Prevalence of chromosomal abnormalities in Sri Lankan women with primary amenorrhea. J Obstet Gynaecol Res. 2013;39(5):991-7.

Ghosh S, Roy S, Pal P, Dutta A, Halder A. Cytogenetic analysis of patients with primary amenorrhea in eastern India. J Obstet Gynaecol. 2018;38(2):270-5.

Koppaka NT, Virulkar SK, Chavan DS, Dalvi RC, Gupta N, Mandava S. Specific chromosomal aberrations in primary amenorrhoea: study on 3776 cases from Indian population. J Obstet Gynecology India. 2019;69(5):457-61.

Ali AB, Indriyati R, Winarni TI, Faradz SM. Cytogenetic analysis and clinical phenotype of primary amenorrhea in Indonesian patients. J Biomed Translational Res. 2018;4(1):22-7.

Chandel D, Sanghavi P, Verma R. Clinical profile and cytogenetic correlations in females with primary amenorrhea. Clin Exp Reprod Med. 2023;50(3):192-9.

Lekha KS, Seena N, Das L, Bhagyam V. Primary amenorrhea in north Kerala: a cytogenetic study. National J Clin Anatomy. 2020;9(3):121-6.

Khan AA, Mabood F, Awan MJ, Khan Z, Ali Q, Riaz S. Conventional cytogenetic analysis of females with primary amenorrhea. BMC J Med Sci. 2024;5(1):48-51.

Thankam U, Hariharan SV, Sarojam S, Syamala R, Alex ST, Ratnamma NV, et al. Proportion and pattern of chromosomal abnormalities in primary amenorrhea in Kerala: a retrospective study. J Clin Diagn Res. 2022;16(11):9-12.

Bagatska NV, Nefidova VE. Chromosomal abnormalities in adolescents girls with primary oligomenorrhea. Україна. 2020(8):26-32.

Halal F, Van Dop C, Lord J. Differential diagnosis in young women with oligomenorrhea and the pseudo-pseudohypoparathyroidism variant of Albright's hereditary osteodystrophy. Am J Med Genet. 1985;21(3):551-68.

Carpenter NJ, Say B, Browning D. Gonadal dysgenesis in a patient with an X; 3 translocation: case report and review. J Med Genet. 1980;17(3):216-21.

Parker R, Ming PL, Rajan R, Goodner DM, Remé G. Clinical and cytogenetic studies of patients with polycystic ovary disease. Am J Obstet Gynecol. 1980;137(6):656-60.

Düzcan F, Atmaca M, Çetin GO, Baǧci H. Cytogenetic studies in patients with reproductive failure. Acta Obstet Gynecol Scand. 2003;82(1):53-6.

Besson MD, Taiarol MD, Fernandes EB, Ghiorzi IB, Nunes MR, Zen PR, et al. Chromosomal abnormalities detected by karyotyping among patients with secondary amenorrhea: a retrospective study. Sao Paulo Med J. 2023;141 (5):e2022426.

Robinson WP, Binkert F, Bernasconi F, Lorda-Sanchez I, Werder EA, Schinzel AA. Molecular studies of chromosomal mosaicism: relative frequency of chromosome gain or loss and possible role of cell selection. Am J Hum Genet. 1995;56 (2):444-51.

Jacobs P, Dalton P, James R, Mosse K, Power M, Robinson D, et al. Turner syndrome: a cytogenetic and molecular study. Ann Hum Genet. 1997;61(Pt 6):471-83.

Otter M, Schrander-Stumpel CT, Curfs LM. Triple X syndrome: a review of the literature. Eur J Hum Genet. 2010;18(3):265-71.

Lin HJ, Ndiforchu F, Patell S. Exstrophy of the cloaca in a 47, XXX child: review of genitourinary malformations in triple‐X patients. Am J Med Genet. 1993;45(6):761-3.

Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L. A review of trisomy X (47, XXX). Orphanet J Rare Dis. 2010;5:8.

Balwan WK, Balwan WK, Saba N, Jamwal KS. Cytogenetic investigation of cases with primary amenorrhea in Jammu Region of Jammu and Kashmir. Int J Zool Res. 2020;10(2):1-8.

El Moussaif N, Haddad N El, Iraqi N, Gaouzi A. 45,X/46,XY mosaicisme: report of five cases and clinical review. Ann Endocrinol (Paris). 2011;72(3):239-43.

Portnoï MF, Aboura A, Tachdjian G, Bouchard P, Dewailly D, Bourcigaux N, et al. Molecular cytogenetic studies of Xq critical regions in premature ovarian failure patients. Hum Reprod. 2006;21(9):2329-34.

Issa NM, Elhady GM. Cytogenetic abnormalities in a sample of females with premature ovarian failure. Middle East Fertil Soc J. 2022;27(1):7.

Veneman TF, Beverstock GC, Exalto N, Mollevanger P. Premature menopause because of an inherited deletion in the long arm of the X-chromosome. Fertil Steril. 1991;55(3):631-3.

Ferreira SI, Matoso E, Pinto M, Almeida J, Liehr T, Melo JB, et al. X-chromosome terminal deletion in a female with premature ovarian failure: haploinsufficiency of X-linked genes as a possible explanation. Mol Cytogenet. 2010;3:14.