Human cells contain 23 pairs of chromosomes that carry our genetic information. One pair, the sex chromosomes (X and Y), determines biological sex. Females have two X chromosomes (XX), while males have one X and one Y (XY). Genetic mosaicism occurs when a person has two or more sets of cells with different genetic makeups originating from a single fertilized egg. This condition can involve the X chromosome, meaning different cells within an individual have a varying number or structure of X chromosomes.
Defining X Chromosome Mosaicism
X chromosome mosaicism means an individual possesses at least two different cell populations, each with a unique X chromosome composition. For instance, a person might have some cells with a 46,XX arrangement and other cells with a single X chromosome (45,X). This results in a mixture of chromosomally normal and abnormal cells throughout the body.
This condition is distinct from the natural process of X-inactivation. In individuals with two X chromosomes, one X is randomly “turned off” in each cell early in development to ensure proper gene expression. While X-inactivation creates a form of functional mosaicism, X chromosome mosaicism refers to differences in the actual number or structure of the X chromosome across cell populations.
The specific combination of cell lines determines the type of mosaicism. For example, some individuals may have a mix of cells with one and two X chromosomes (45,X/46,XX), while others might have a combination of cells with two and three X chromosomes (46,XX/47,XXX).
The Origins of X Chromosome Mosaicism
X chromosome mosaicism is not inherited but arises from spontaneous errors during cell division, or mitosis, in early embryonic development. These mistakes happen after fertilization, meaning the initial fertilized egg, or zygote, is chromosomally normal. As the embryo’s cells divide, an error can create a new cell line with a different number of X chromosomes.
One common mechanism is nondisjunction, which occurs when chromosomes fail to separate properly as a cell divides. This results in one daughter cell receiving an extra X chromosome while the other is missing one, creating two distinct cell lines.
Another cause is anaphase lag. During cell division, a chromosome may move too slowly and be left out of the newly formed cell’s nucleus. This lagging chromosome is subsequently lost, resulting in one cell with a missing X chromosome and another with the correct number.
Key Types of X Chromosome Mosaicism
A frequently identified form is mosaic Turner syndrome, affecting an estimated 30% to 40% of individuals with the syndrome. In this variation, some cells have a single X chromosome (45,X), while other cells contain the typical two X chromosomes (46,XX). This mixture often results in milder features compared to the non-mosaic form.
Another recognized type is mosaic Triple X syndrome (46,XX/47,XXX). Individuals with this condition have some cells with the usual pair of X chromosomes and others with an extra X. The associated effects are often subtle and may include tall stature or learning difficulties, with many having no noticeable symptoms.
Mosaicism can also occur in males, with mosaic Klinefelter syndrome (46,XY/47,XXY) being a notable example. In this case, some cells have the standard XY configuration, while others have an additional X chromosome. People with this mosaic form may show milder signs than those with the extra X in all their cells. Mosaicism can also involve structural alterations, such as deletions or a ring-shaped X chromosome.
Range of Physical and Developmental Effects
The clinical presentation of X chromosome mosaicism is highly variable, ranging from no apparent symptoms to health issues. This variability is influenced by the specific type of chromosomal difference, such as a missing versus an extra X chromosome.
The proportion of cells containing the chromosomal anomaly also plays a role; a higher percentage of affected cells can lead to more pronounced effects. The distribution of these cell lines throughout the body’s tissues is another determinant. For example, if the chromosomally different cells are primarily in the ovaries, the main impact might be on fertility, while other traits remain unaffected.
Identifying X Chromosome Mosaicism
X chromosome mosaicism is identified through genetic testing, often prompted by clinical signs such as developmental delays, physical features, or fertility challenges. In some cases, the condition is discovered incidentally during prenatal testing or other genetic analyses.
The primary diagnostic tool is a karyotype, which is a laboratory analysis of a person’s chromosomes from a blood sample. Technicians examine a number of individual cells to identify their chromosomal makeup. Finding more than one cell line with different X chromosome compositions confirms a diagnosis.
If mosaicism is suspected but not found in a blood test, further investigation may be required. Because the distribution of mosaic cells can differ between tissues, a sample from another area, such as skin or cheek cells, might be analyzed. Techniques like Fluorescence In Situ Hybridization (FISH) can also be used to screen a larger number of cells, sometimes offering a more sensitive detection method.