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Crit Rev Clin Lab Sci. 2018 Sep;55(6):432-442. doi: 10.1080/10408363.2018.1488805. Epub 2018 Jul 23.

Mosaicism in autoinflammatory diseases: Cryopyrin-associated periodic syndromes (CAPS) and beyond. A systematic review.

Author information

1
a Department of Medical Genetics, Rare Diseases and Personalized Medicine, CHU Montpellier , Stem Cells, Cellular Plasticity, Regenerative Medicine and Immunotherapies, INSERM, Univ Montpellier , Montpellier , France.
2
b Pediatric Nephrology, Rheumatology, Dermatology , University of Lyon , Lyon , France.
3
c National Amyloidosis Centre , Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine , London , UK.
4
d Department of Internal Medicine , Hôpitaux Privés , Metz , France.
5
e Internal Medicine Department , Haut-Lévêque Hospital , Pessac , France.
6
f Pediatric Rheumatology Unit , Centre for Child Health, Sir Ganga Ram Hospital , New Delhi , India.
7
g Hemato Onco Pediatrics Department , CHRU Nancy , Vandoeuvre les Nancy , France.
8
h Department of Biostatistics , University Hospital of Montpellier , Montpellier , France.

Abstract

Autoinflammatory diseases (AIDs) are conditions related to defective regulation of the innate immune system. Sanger sequencing of the causative genes has long been the reference for confirming the diagnosis. However, for many patients with a typical AID phenotype, the genetic cause remains unknown. A pioneering study in 2005 demonstrated mosaicism in patients with cryopyrin-associated periodic syndromes (CAPS); the authors found somatic mosaicism in 69% of their cohort of Sanger-negative CAPS patients. We aim to address the extent to which mosaicism contributes to the etiology of AIDs and its impact on phenotype. We retrieved English-language publications reporting mosaicism in AIDs by querying PubMed with no restriction on date and we surveyed French reference centers. We provide a comprehensive clinical and genetic picture of mosaicism in AIDs. We estimate that the proportion of CAPS-like patients presenting mosaicism ranges from 0.5% to 19%. We also discuss the possible links between the proportion of mutated alleles and various clinical features. This review reevaluates the contribution of mosaic DNA variants in CAPS. Mosaicism may be more common than anticipated in other AIDs. No significant difference was demonstrated between variant allele frequency and clinical phenotype. Such knowledge has implications for the development of guidelines for genetic diagnosis, genetic counseling of affected families and effective patient care.

KEYWORDS:

CAPS; autoinflammatory disease; mosaicism; systematic review

PMID:
30035647
DOI:
10.1080/10408363.2018.1488805
[Indexed for MEDLINE]

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