X chromosome loss and ageing.

Area of Science:

• Cytogenetics
• Human Genetics
• Reproductive Biology

Background:

• Interpreting low-level 45,X cell lines in adult females is challenging.
• Limited recent data exists on X chromosome loss and its relation to aging.

Purpose of the Study:

• To prospectively investigate the relationship between X chromosome loss and female aging.
• To establish age-related baseline rates for X chromosome loss.
• To assess the association between 45,X cells and spontaneous abortion.

Main Methods:

• Cytogenetic screening of 19,650 cells from 655 females aged 0-80 years.
• Statistical analysis to determine the relationship between X chromosome loss frequency and age.
• Comparison of 45,X cell frequency in women with and without a history of spontaneous abortion.

Main Results:

• X chromosome loss frequency ranged from 0.07% (<16 years) to 7.3% (>65 years).
• A highly significant quadratic relationship was observed between X chromosome loss and aging (P < 0.00001).
• No significant difference in 45,X cell frequency was found between women with and without spontaneous abortions.

Conclusions:

• Age-related baseline rates of X chromosome loss can now be graphically represented.
• These findings aid diagnostic cytogenetics laboratories in interpreting 45,X cell lines.
• An excess of 45,X cells is not associated with pregnancy loss in this population.