Heterochromatin extension: a possible cytogenetic fate of primary amenorrhea along with normal karyotype

Abstract

Primary amenorrhoea (PA) is considered to be one of the challenging and taxing problems for the gynaecologist. Previous studies suggested that different numerical and structural chromosome abnormalities are associated with this. Heterochromatin polymorphisms are considered to be normal variant but considering the recent research on crucial cellular effects of heterochromatin, we have aimed to find out the prevalence of heteromorphism along with other standard chromosomal abnormalities. This was an observational study which was conducted in Diamond Harbour Govt. Medical College and Hospital, West Bengal during March 2019–February 2021. Clinical features of 178 patients were noted and peripheral venous blood was taken following informed consent. This comprehensive study reveals that there are 10.11% of the females among 178 females having a heterochromatin extension which is significantly high. We hence suggest that heteromorphism may be associated with ovarian dysfunction leading to amenorrhoea as the region of heterochromatin acts as a key part in chromosome structure, histone modification and gene regulation. Analysis at the molecular level may be needed to unveil any relationship between heteromorphism and PA.

Impact Statement

• What is already known on this subject? Primary amenorrhoea (PA) is a menstrual abnormality found in females with the prevalence of 1–3%. It may be associated with different types of numerical and structural chromosomal anomalies. Among them Turner’s syndrome (pure and in variant form) is the commonest chromosomal aberration associated with PA. Some patients with PA are found to have a normal karyotype with heterochromatin extension on the large arm (q) of either chromosome 9 or chromosome 16. Chromosomal polymorphism with increase in heterochromatin region consists of highly repetitive sequences of satellite DNA, which normally does not encode any protein and thus considered to be a normal variant.

• What do the results of this study add? This comprehensive study reveals that there are 10.11% of the females among 178 females having a heterochromatin extension which is significantly high. PA and certain association of phenotypical stigmata like short stature in these patients with heterochromatin extension can be explained on the basis of histone modification and gene regulation by heterochromatin.

• What are the implications of these findings for clinical practice and/or further research? We will be able to know about involved transcription factors those are responsible for the histone modification directly linked to the heterochromatin extension by further molecular study. That will definitely help to find out the reason for PA as well as implementation of gene therapy in these cases.

Keywords:

• Primary amenorrhoea
• structural abnormality
• heterochromatin polymorphism

Acknowledgements

We like to admire the cooperation of Dr. Somajita Chakrabarty (Professor and Head, Department of Gynaecology and Obstetrics, Diamond Harbour Govt. Medical College and Hospital) and her team for recruiting primary amenorrheic females for our research-based study. Ms. Shanoli Ghosh and Dr. Ajanta Halder contributed equally to study different primary amenorrheic patients on the basis of their phenotypic features.

Disclosure statement

We declare that we have no conflict of interest.

Additional information

Funding

This project was funded by Department of Science, Technology & Biotechnology (DSTBT), Govt. of West Bengal, India.