From curiosity to clinical relevance: Rethinking genetic mosaicism.

A review of mosaicism, its detection by ultra-deep sequencing and its consequences for genetic testing and counselling

A recent international case — a sperm donor who unknowingly transmitted a pathogenic TP53 variant to numerous offspring — has renewed attention to germline mosaicism and its clinical implications. This review traces the evolution of mosaicism from simple observations of segmental phenotypes to its recognition as a common biological phenomenon. Ultra-deep sequencing technologies have transformed its detection and clarified its significance. Mosaicism challenges classic genotype-phenotype relationships, contributes to variable expressivity and complicates genetic testing and counselling.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A review rather than new data, but the angle is highly communicable and educational: mosaicism, long a curiosity, is becoming a concrete issue for testing and counselling, in cancer genetics and beyond. Useful for raising awareness of the limits of standard blood sequencing and the value of deep sequencing in selected situations.

Analysis by Dr Thibaut Benquey