Understanding mosaicism: A primer for clinicians

ABSTRACT: Genetic mosaicism refers to the presence of two or more genetically distinct cell populations derived from a single zygote, resulting from post-zygotic genetic or epigenetic variation. This phenomenon contributes to diverse clinical presentations across a broad range of disorders and holds significant implications for diagnosis, inheritance risk, and clinical management. This article provides an overview of mosaicism from a clinical perspective, emphasizing its relevance for nurse practitioners. Two types of mosaicism are described with representative conditions: chromosomal mosaicism by trisomy 21 and germline mosaicism illustrated by Duchenne muscular dystrophy. Each clinical case demonstrates how the timing, location, and nature of mosaic variants influence phenotype, recurrence risk, and detection. Clinical pearls are included for each case emphasizing important take-aways for practice. Understanding these mechanisms is essential for interpretation of genetic testing, risk assessment, and counseling and education of affected individuals and their families.