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Genetic Aspects of Investigating and Understanding Autoinflammation

  • Isabella CeccheriniEmail author
  • Marta Rusmini
  • Juan Ignacio Arostegui
Chapter

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.

Keywords

Next generation sequencing (NGS) Gene discovery Mutation screening NGS-based gene panel Comparative genomic hybridization (CGH) Gene expression Real-time polymerase chain reaction (rtPCR) Gene mosaicism Post-zygotic mutations Amplicon-based deep sequencing 

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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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Isabella Ceccherini
    • 1
    Email author
  • Marta Rusmini
    • 1
  • Juan Ignacio Arostegui
    • 2
  1. 1.U.O.C. Genetica Medica, Istituto Giannina GasliniGenoaItaly
  2. 2.Department of ImmunologyIDIBAPS, Hospital ClínicBarcelonaSpain

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