monogén

Monogén, or monogenic, refers to traits or diseases that are caused by mutations in a single gene. In this sense, the phenotype arises primarily from variation at one genetic locus, although environmental factors and other genetic modifiers can influence the severity and presentation of the condition.

Monogenic traits are typically inherited following Mendelian patterns: autosomal dominant, autosomal recessive, or X-linked. In autosomal dominant disorders, a single pathogenic variant is usually sufficient to cause disease; in autosomal recessive disorders, two copies of the variant are needed; X-linked conditions often affect males more severely or earlier. Penetrance and expressivity can vary, so some individuals carrying the variant may be asymptomatic (reduced penetrance) or show a range of symptoms (variable expressivity). De novo mutations can also generate monogenic diseases without a family history.

Common examples of monogenic disorders include cystic fibrosis (CFTR gene, autosomal recessive), phenylketonuria (PAH, autosomal recessive), Huntington’s disease (HTT, autosomal dominant), Marfan syndrome (FBN1, autosomal dominant), and sickle cell disease (HBB, autosomal recessive). These conditions illustrate how a single gene alteration can lead to a characteristic clinical syndrome, even though outcomes can vary among individuals.

Diagnosis typically involves genetic testing to identify pathogenic variants in a single gene. Approaches include targeted gene panels, exome sequencing, or genome sequencing, complemented by newborn screening, prenatal testing, and cascade testing for relatives.

Clinical implications include genetic counseling and assessment of recurrence risk based on inheritance pattern. Management is disease-specific and may include surveillance, medical or surgical treatment, and, in some cases, emerging gene-targeted therapies or experimental gene-editing approaches. The term monogén is used across languages (e.g., monogènic/monogénico) to describe this genetic concept.