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Textbook of Autoinflammation pp 19–48Cite as

Genetic Aspects of Investigating and Understanding Autoinflammation

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Abstract

At present, more than 30 different autoinflammatory diseases have been described at molecular and genetic level. The importance of genetic tests to reach a definitive diagnosis has become evident during the past few years. In parallel to the description of these diseases, several technical changes have occurred that have revolutionized the field of human genetics. Ten years ago, the gold-standard method for genetic studies was the Sanger method of DNA sequencing. Currently, studies based on next generation sequencing (NGS) methods are the standard methods in most genetic laboratories around the world. NGS makes it possible to achieve a diagnosis both by analysis of single families with extremely rare conditions, thus identifying new genes, or simultaneous genotyping of multiple genes in groups of patients. Moreover, in the past few years, different insights demonstrated an unexpected role of post-zygotic mutations and gene mosaicism in the pathogenesis of some monogenic autoinflammatory diseases. The availability of NGS methods in the clinics allows detection of (new) monogenic diseases in a growing number of previously undiagnosed patients with no familial history. This has resulted in the increased awareness of the clinical diversity of these diseases, best therapeutic approaches and follow-up schemes for the patients and appropriate genetic counseling for families.

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Abbreviations

ACMG:

America College of Medical Genetics and Genomics

CAPS:

Cryopyrin-associated periodic syndrome

CGH:

Comparative genomic hybridization

CINCA:

Chronic infantile neurological, cutaneous and articular

CNV:

Copy number variations

DADA2:

Deficiency of adenosine deaminase 2

ddNTP:

Dideoxynucleotide

DIRA:

Deficiency of IL-1 receptor antagonist

DSAP:

Disseminated superficial actinic porokeratosis

FCAS:

Familial cold autoinflammatory syndrome

FMF:

Familial Mediterranean fever

IL:

Interleukin

InDels:

Insertions or deletions

JMP:

Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome

LPS:

Lipopolysaccharide

MKD:

Mevalonate kinase deficiency

MWS:

Muckle Wells syndrome

NGS:

Next generation sequencing

NOMID:

Neonatal-onset multisystem inflammatory disease

PCR:

Polymerase chain reaction

PID:

Primary immunodeficiency diseases

POADS:

Postaxial acrofacial dysostosis

SAVI:

STING-associated vasculopathy with onset in infancy

SNP:

Single nucleotide polymorphism

SNV:

Single nucleotide variant

STING:

Stimulator of interferon genes

TGF:

Transforming growth factor

TNF:

Tumor necrosis factor

TRAPS:

TNF receptor-associated periodic syndrome

VUS:

Variant of uncertain significance

WES:

Whole exome sequencing

WGS:

Whole genome sequencing

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Authors and Affiliations

  1. U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genoa, Italy

    Isabella Ceccherini & Marta Rusmini

  2. Department of Immunology, IDIBAPS, Hospital Clínic, Barcelona, Spain

    Juan Ignacio Arostegui

Authors
  1. Isabella Ceccherini
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  2. Marta Rusmini
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  3. Juan Ignacio Arostegui
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Correspondence to Isabella Ceccherini .

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Editors and Affiliations

  1. Pediatric Rheumatology Unit, Shaare Zedek Medical Center and Hebrew University, Jerusalem, Israel

    Philip J. Hashkes

  2. Department Paediatrics, Division of Rheumatology, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada

    Ronald M. Laxer

  3. Department of Internal Medicine, Radboudumc Expertisecenter for Immunodeficiency and Autoinflammation, Radboud University Medical Center, Nijmegen, The Netherlands

    Anna Simon

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Ceccherini, I., Rusmini, M., Arostegui, J.I. (2019). Genetic Aspects of Investigating and Understanding Autoinflammation. In: Hashkes, P., Laxer, R., Simon, A. (eds) Textbook of Autoinflammation. Springer, Cham. https://doi.org/10.1007/978-3-319-98605-0_2

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  • DOI: https://doi.org/10.1007/978-3-319-98605-0_2

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