Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis

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https://doi.org/10.1016/j.ajhg.2011.07.022
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Keywords

Child, Child, Preschool, Female, Genetic Predisposition to Disease, Humans, Immunity, Innate, Interleukins, Male, Middle Aged, Models, Molecular, Mutation, Missense, Pedigree, Psoriasis, Sequence Analysis, DNA

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Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. / Onoufriadis, Alexandros; Simpson, Michael A.; Pink, Andrew E. et al.
In: American Journal of Human Genetics, Vol. 89, No. 3, 09.09.2011, p. 432-437.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Onoufriadis, A, Simpson, MA, Pink, AE, Di Meglio, P, Smith, CH, Pullabhatla, V, Knight, J, Spain, SL, Nestle, FO, Burden, AD, Capon, F, Trembath, RC & Barker, JNWN 2011, 'Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis', American Journal of Human Genetics, vol. 89, no. 3, pp. 432-437. https://doi.org/10.1016/j.ajhg.2011.07.022

APA

Onoufriadis, A., Simpson, M. A., Pink, A. E., Di Meglio, P., Smith, C. H., Pullabhatla, V., Knight, J., Spain, S. L., Nestle, F. O., Burden, A. D., Capon, F., Trembath, R. C., & Barker, J. N. W. N. (2011). Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. American Journal of Human Genetics, 89(3), 432-437. https://doi.org/10.1016/j.ajhg.2011.07.022

Vancouver

Onoufriadis A, Simpson MA, Pink AE, Di Meglio P, Smith CH, Pullabhatla V et al. Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. American Journal of Human Genetics. 2011 Sept 9;89(3):432-437. doi: 10.1016/j.ajhg.2011.07.022

Author

Onoufriadis, Alexandros ; Simpson, Michael A. ; Pink, Andrew E. et al. / Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. In: American Journal of Human Genetics. 2011 ; Vol. 89, No. 3. pp. 432-437.

Bibtex

@article{ed3a6d9f76144220af22cd9ff484bb85,

title = "Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis",

abstract = "Generalized pustular psoriasis (GPP) is a rare and yet potentially lethal clinical variant of psoriasis, characterized by the formation of sterile cutaneous pustules, neutrophilia, fever and features of systemic inflammation. We sequenced the exomes of five unrelated individuals diagnosed with GPP. Nonsynonymous, splice-site, insertion, and deletion variants with an estimated population frequency of <0.01 were considered as candidate pathogenic mutations. A homozygous c.338C>T (p.Ser113Leu) missense substitution of IL36RN was identified in two individuals, with a third subject found to be a compound heterozygote for c.338C>T (p.Ser113Leu) and a c.142C>T (p.Arg48Trp) missense substitution. IL36RN (previously known as IL1F5) encodes an IL-1 family receptor antagonist, which opposes the activity of the IL-36A and IL-36G innate cytokines. Homology searches revealed that GPP mutations alter evolutionarily conserved residues. Homozygosity for the c.338C>T (p.Ser113Leu) variant is associated with an elevated proinflammatory response following ex vivo stimulation with IL36A. These findings suggest loss of function of IL36RN as the genetic basis of GPP and implicate innate immune dysregulation in this severe episodic inflammatory disease, thereby highlighting IL-1 signaling as a potential target for therapeutic intervention.",

keywords = "Child, Child, Preschool, Female, Genetic Predisposition to Disease, Humans, Immunity, Innate, Interleukins, Male, Middle Aged, Models, Molecular, Mutation, Missense, Pedigree, Psoriasis, Sequence Analysis, DNA",

author = "Alexandros Onoufriadis and Simpson, {Michael A.} and Pink, {Andrew E.} and {Di Meglio}, Paola and Smith, {Catherine H.} and Venu Pullabhatla and Jo Knight and Spain, {Sarah L.} and Nestle, {Frank O.} and Burden, {A. David} and Francesca Capon and Trembath, {Richard C.} and Barker, {Jonathan N. W. N.}",

year = "2011",

month = sep,

day = "9",

doi = "10.1016/j.ajhg.2011.07.022",

language = "English",

volume = "89",

pages = "432--437",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "3",

}

RIS

TY - JOUR

T1 - Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis

AU - Onoufriadis, Alexandros

AU - Simpson, Michael A.

AU - Pink, Andrew E.

AU - Di Meglio, Paola

AU - Smith, Catherine H.

AU - Pullabhatla, Venu

AU - Knight, Jo

AU - Spain, Sarah L.

AU - Nestle, Frank O.

AU - Burden, A. David

AU - Capon, Francesca

AU - Trembath, Richard C.

AU - Barker, Jonathan N. W. N.

PY - 2011/9/9

Y1 - 2011/9/9

N2 - Generalized pustular psoriasis (GPP) is a rare and yet potentially lethal clinical variant of psoriasis, characterized by the formation of sterile cutaneous pustules, neutrophilia, fever and features of systemic inflammation. We sequenced the exomes of five unrelated individuals diagnosed with GPP. Nonsynonymous, splice-site, insertion, and deletion variants with an estimated population frequency of <0.01 were considered as candidate pathogenic mutations. A homozygous c.338C>T (p.Ser113Leu) missense substitution of IL36RN was identified in two individuals, with a third subject found to be a compound heterozygote for c.338C>T (p.Ser113Leu) and a c.142C>T (p.Arg48Trp) missense substitution. IL36RN (previously known as IL1F5) encodes an IL-1 family receptor antagonist, which opposes the activity of the IL-36A and IL-36G innate cytokines. Homology searches revealed that GPP mutations alter evolutionarily conserved residues. Homozygosity for the c.338C>T (p.Ser113Leu) variant is associated with an elevated proinflammatory response following ex vivo stimulation with IL36A. These findings suggest loss of function of IL36RN as the genetic basis of GPP and implicate innate immune dysregulation in this severe episodic inflammatory disease, thereby highlighting IL-1 signaling as a potential target for therapeutic intervention.

AB - Generalized pustular psoriasis (GPP) is a rare and yet potentially lethal clinical variant of psoriasis, characterized by the formation of sterile cutaneous pustules, neutrophilia, fever and features of systemic inflammation. We sequenced the exomes of five unrelated individuals diagnosed with GPP. Nonsynonymous, splice-site, insertion, and deletion variants with an estimated population frequency of <0.01 were considered as candidate pathogenic mutations. A homozygous c.338C>T (p.Ser113Leu) missense substitution of IL36RN was identified in two individuals, with a third subject found to be a compound heterozygote for c.338C>T (p.Ser113Leu) and a c.142C>T (p.Arg48Trp) missense substitution. IL36RN (previously known as IL1F5) encodes an IL-1 family receptor antagonist, which opposes the activity of the IL-36A and IL-36G innate cytokines. Homology searches revealed that GPP mutations alter evolutionarily conserved residues. Homozygosity for the c.338C>T (p.Ser113Leu) variant is associated with an elevated proinflammatory response following ex vivo stimulation with IL36A. These findings suggest loss of function of IL36RN as the genetic basis of GPP and implicate innate immune dysregulation in this severe episodic inflammatory disease, thereby highlighting IL-1 signaling as a potential target for therapeutic intervention.

KW - Child

KW - Child, Preschool

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Immunity, Innate

KW - Interleukins

KW - Male

KW - Middle Aged

KW - Models, Molecular

KW - Mutation, Missense

KW - Pedigree

KW - Psoriasis

KW - Sequence Analysis, DNA

U2 - 10.1016/j.ajhg.2011.07.022

DO - 10.1016/j.ajhg.2011.07.022

M3 - Journal article

C2 - 21839423

VL - 89

SP - 432

EP - 437

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 3

ER -

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