Format

Send to

Choose Destination
Nat Rev Genet. 2019 Jun 11. doi: 10.1038/s41576-019-0139-x. [Epub ahead of print]

Somatic genetic rescue in Mendelian haematopoietic diseases.

Author information

1
INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Equipe Labellisée Ligue contre le Cancer, Paris, France. patrick.revy@inserm.fr.
2
Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France. patrick.revy@inserm.fr.
3
APHP Service de Génétique, Hôpital Bichat, Paris, France.
4
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
5
Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France.
6
Collège de France, Chaire de médecine expérimentale, Paris, France.
7
Unité d'immunologie, hématologie et rhumatologie pédiatrique, hôpital Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
8
INSERM UMR 1163, Imagine Institute, Paris, France.

Abstract

Somatic mutations occur spontaneously in normal individuals and accumulate throughout life. These genetic modifications contribute to progressive ageing phenotypes and are directly involved in cancer development. However, a growing number of studies of Mendelian haematopoietic disorders indicate that somatic genetic events can offset the pathogenic effect of germline mutations at the cellular level, leading to genetic mosaicism and, in some cases, resulting in a milder disease phenotype. Notably, spontaneous genetic events that confer a positive effect on cells do not always benefit the individual, for whom the effects can be neutral or even clinically detrimental. These somatic genetic rescue events have important diagnostic, therapeutic and clinical consequences and constitute valuable models for studying the differentiation and/or homeostasis of haematopoietic lineages.

PMID:
31186537
DOI:
10.1038/s41576-019-0139-x

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center