From the Guidelines
Mosaicism is the presence of cells of multiple different genotypes within a single animal or cell population. This condition occurs when genetic mutations arise during early embryonic development, resulting in some cells carrying one genetic makeup while others have a different genetic composition 1. The severity of mosaicism depends on when the mutation occurs during development, which cell types are affected, and what percentage of cells contain the mutation.
Key Points
- Mosaicism can cause various medical conditions with varying symptoms depending on which tissues contain the abnormal cells.
- For example, skin mosaicism might appear as patches of differently pigmented skin, while mosaicism affecting the brain could cause neurological symptoms.
- This condition explains why some genetic disorders show varying degrees of expression or why some genetic tests may yield inconclusive results if the sampled tissue doesn't contain the mutated cells.
- Detection of mosaicism can be challenging, and methods such as microarray analysis, fluorescence in situ hybridization, and conventional cytogenetic analysis may be used to identify mosaicism 1.
- The level of detectable mosaicism can vary depending on the size and region of the genome, copy number state, DNA quality, and data quality.
- Reproductive counseling is important for individuals with mosaicism, as they may have a higher risk of transmitting the mutation to their offspring 1.
- In some cases, individuals with somatic mosaicism may be at increased risk for tumor development, and surveillance recommendations may be necessary 1.
From the Research
Definition of Mosaicism
- Mosaicism refers to the presence of two or more cell populations with distinct genotypes in an individual, derived from a single fertilized egg 2, 3, 4, 5.
- This condition occurs when there is a mutation during mitotic cell divisions after fertilization and zygote formation, resulting in genetic variation among cell lines 2.
- Mosaicism can involve whole chromosomes, structural or copy-number variants, small or single-nucleotide variants, or epigenetic variants 2.
Types and Detection of Mosaicism
- There are different types of mosaicism, including germline, gonosomal, and somatic genomic mosaicism, each with distinct characteristics and implications 6.
- The detection of mosaicism can be challenging, and it often requires multiple test samples and orthogonal methods of detection 4.
- Next-generation sequencing technologies have improved the detection rate of mosaicism, but revisions in current diagnostic protocols are necessary to increase the detection rate of unrevealed mosaicism events 3.
Clinical Implications of Mosaicism
- Mosaicism has been implicated in hundreds of genetic diseases, affecting every organ system, and can result in a range of phenotypic effects, from severe to mild 5.
- The clinical manifestations of mosaicism depend on the differentiation status of the mutated cell and the affected cell type 6.
- Mosaicism can also increase the risk of transmitting a pathogenic genotype, and accurate diagnosis and counseling are essential for affected individuals and their families 4, 5.