Adult onset autoimmune lymphoproliferative syndrome due to somatic <scp>FAS</scp> mutation

García, Gema María García; Dacal, J. C. Bureo; Pineda, Sara; Izaguirre, R.

doi:10.1111/imj.12714

Cited by 5 publications

(3 citation statements)

References 5 publications

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“…The somatic mutation was either acquired on the second FAS allele or occurred through somatic uniparental disomy (a situation where both chromosomes are derived from 1 parent). Somatic mutations detected in FAS in DNT cells (either dominant negative or haploinsufficiency) were also described in other reports of ALPS-sFAS in adults (43 and 48 years at disease onset) ( 15 , 107 ).…”

Section: Genetic Defects Associated With Adult-onset Ieisupporting

confidence: 69%

Monogenic Adult-Onset Inborn Errors of Immunity

et al. 2021

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Inborn errors of immunity (IEI) are a heterogenous group of disorders driven by genetic defects that functionally impact the development and/or function of the innate and/or adaptive immune system. The majority of these disorders are thought to have polygenic background. However, the use of next-generation sequencing in patients with IEI has led to an increasing identification of monogenic causes, unravelling the exact pathophysiology of the disease and allowing the development of more targeted treatments. Monogenic IEI are not only seen in a pediatric population but also in adulthood, either due to the lack of awareness preventing childhood diagnosis or due to a delayed onset where (epi)genetic or environmental factors can play a role. In this review, we discuss the mechanisms accounting for adult-onset presentations and provide an overview of monogenic causes associated with adult-onset IEI.

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Section: Genetic Defects Associated With Adult-onset Ieisupporting

confidence: 69%

Monogenic Adult-Onset Inborn Errors of Immunity

et al. 2021

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“…in a 55-year-old patient with chronic lymphadenopathy as the only manifestation and only somatic mutation of FAS that did not require treatment, [14] we can argue that sometimes two mutations may be necessary to cause the complete manifestation of the syndrome. More than half of patients with ALPS need immunosuppressive treatment for manifestations of autoimmunity, high-dose systemic steroid schemes are needed for short cycles [15].…”

Section: Autoimmune Lymphoproliferative Syndrome With Somatic Mutatiomentioning

confidence: 92%

Phenocopies: Mimics of Inborn Errors of Immunity

Alonso-Bello¹,

Espinosa‐Padilla²,

Temix-Delfin³

et al. 2020

OALib

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A phenocopy is defined as a clinical non-inherited phenotype in an individual, with environmental induction, which is identical to the genetically determined phenotype of another. Until February 2017, the IUIS (International Union of Immunological Societies) reported in its classification 354 innate immunity errors and a final group (classification table IX) with conditions that are not part of the innate alterations and are called phenocopies. These are classified into two types, the associated with somatic mutations and those associated with auto-antibodies. The phenotypes that occur by any of the mechanisms mentioned are complex and varied. It is necessary to know the clinical manifestations of the pathologies classified in this group to enrich the possible differential diagnoses in individuals with suspected immunodeficiency.

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“…Somatic FAS mutations are the second most common genetic etiology of this disease (ALPS-sFAS) [ [35] , [36] , [37] , [38] ]. The somatic mutations likely appear during the embryologic development, in hematopoietic progenitors or earlier, and confers a selective advantage to the mutated cells.…”

Section: Somatic Dominant Mutationsmentioning

confidence: 99%

The genetic landscape of the FAS pathway deficiencies

2021

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Dysfunction of the FAS-FASLG pathway causes a lymphoproliferative disorder with autoimmunity called Autoimmune lymphoproliferative syndrome (ALPS) mainly caused by FAS mutations. The goal of this review is to describe the genetic bases of the autoimmune lymphoproliferative syndrome and to underline their genetic complexity with the contribution of both germline and somatic events accounting for the variable clinical penetrance of the FAS mutations. Starting from the cohort of patients studied in the French cohort (>165 cases), we also reviewed the literature cases in order to depict a full description of the mutations affecting the FAS-FASLG pathway involved in the outcome of this rare non-malignant and non-infectious pediatric lymphoproliferative disease. We also discussed the variable clinical penetrance associated with mutations affecting the extracellular domain of the protein. Such non-penetrant germline mutations are frequently associated with an additional somatic event impacting the second allele of FAS . Moreover, the uncomplete clinical penetrance associated with mutations affecting the intracellular domain of FAS, in patient lacking additional FAS somatic event, suggested a potential digenic inheritance with a FAS mutation accompanied by a genetic modifier possibly impacting another player of the lymphocytes homeostasis (affecting the survival, activation or apoptosis of the peripheral leukocytes).

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Adult onset autoimmune lymphoproliferative syndrome due to somatic FAS mutation

Cited by 5 publications

References 5 publications

Monogenic Adult-Onset Inborn Errors of Immunity

Monogenic Adult-Onset Inborn Errors of Immunity

Phenocopies: Mimics of Inborn Errors of Immunity

The genetic landscape of the FAS pathway deficiencies

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