Identification of a homozygous PSTPIP1 mutation in a patient with a PAPA-like syndrome responding to canakinumab treatment

Alexandra Geusau, Nadine Mothes-Luksch, Hesam Nahavandi, Winfried F. Pickl, Carol A. Wise, Zahra Pourpak, Elisabeth Ponweiser, Leopold Eckhart, Raute Sunder-Plassmann

Research output: Contribution to journalArticle

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Abstract

Background: Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome (OMIM 604416) is a rare autosomal dominant inherited autoinflammatory syndrome characterized by pyogenic sterile arthritis and less frequently accompanied by pyoderma gangrenosum and acne. It is associated with dominant missense mutations in the proline-serine-threonine phosphatase- interacting protein 1 gene (PSTPIP1) located on chromosome 15. The patient was diagnosed as having features of a PAPA-like syndrome in which cutaneous manifestations, such as pyoderma gangrenosum and acne fulminans, predominated. Observations: Sequencing of the PSTPIP1 gene was performed in the patient and his extended family. The patient's DNA analysis revealed a homozygous nucleotide exchange c.773G>C in the PSTPIP1 gene, leading to the substitution of glycine 258 by alanine (p.Gly258Ala), a previously reported heterozygous polymorphism. Heterozygous changes were identified in both of the patient's parents and in 7 other family members, all of whom were asymptomatic. The patient was treated with canakinumab, a human anti-interleukin 1β monoclonal antibody, which led to rapid remission of the symptoms. Conclusions: To our knowledge, this is the first reported case of the resolution of dermatological symptoms associated with a PAPA-like syndrome using canakinumab treatment. Further study of the p.Gly258Ala variant is warranted to determine whether this mutation has a role in causing an apparently recessive cutaneous syndrome resembling PAPA syndrome.

Original languageEnglish (US)
Pages (from-to)209-215
Number of pages7
JournalJAMA Dermatology
Volume149
Issue number2
DOIs
StatePublished - Feb 2013

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Protein Phosphatase 1
Phosphoprotein Phosphatases
Proline
Mutation
Genes
Pyoderma Gangrenosum
Acne Vulgaris
Therapeutics
Genetic Databases
Skin Manifestations
Chromosomes, Human, Pair 15
Missense Mutation
Interleukin-1
Alanine
Glycine
Arthritis
canakinumab
Pyogenic arthritis, pyoderma gangrenosum, and acne
Nucleotides
Parents

ASJC Scopus subject areas

  • Dermatology

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Identification of a homozygous PSTPIP1 mutation in a patient with a PAPA-like syndrome responding to canakinumab treatment. / Geusau, Alexandra; Mothes-Luksch, Nadine; Nahavandi, Hesam; Pickl, Winfried F.; Wise, Carol A.; Pourpak, Zahra; Ponweiser, Elisabeth; Eckhart, Leopold; Sunder-Plassmann, Raute.

In: JAMA Dermatology, Vol. 149, No. 2, 02.2013, p. 209-215.

Research output: Contribution to journalArticle

Geusau, A, Mothes-Luksch, N, Nahavandi, H, Pickl, WF, Wise, CA, Pourpak, Z, Ponweiser, E, Eckhart, L & Sunder-Plassmann, R 2013, 'Identification of a homozygous PSTPIP1 mutation in a patient with a PAPA-like syndrome responding to canakinumab treatment', JAMA Dermatology, vol. 149, no. 2, pp. 209-215. https://doi.org/10.1001/2013.jamadermatol.717
Geusau, Alexandra ; Mothes-Luksch, Nadine ; Nahavandi, Hesam ; Pickl, Winfried F. ; Wise, Carol A. ; Pourpak, Zahra ; Ponweiser, Elisabeth ; Eckhart, Leopold ; Sunder-Plassmann, Raute. / Identification of a homozygous PSTPIP1 mutation in a patient with a PAPA-like syndrome responding to canakinumab treatment. In: JAMA Dermatology. 2013 ; Vol. 149, No. 2. pp. 209-215.
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