title: Variations of the perforin gene in patients with chronic inflammatory demyelinating polyradiculoneuropathy.
abstract: Perforin (PRF) has a key role in the function of cytotoxic T and natural killer cells. Rare variations of PRF1 predispose to autoimmunity. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, involving defective lymphocyte apoptosis. The aim of this study was to investigate the role of PRF1 in CIDP. The entire coding region of PRF1 was sequenced in 94 patients and 158 controls. We found three missense variations leading to amino acid substitutions and one nonsense variation resulting in a premature stop codon. All variations would decrease PRF activity. Their overall frequency was significantly higher in patients than in controls (odds ratio (OR)=4.47). The most frequent variation was p.Ala91Val (OR=3.92) previously associated with other autoimmune diseases. Clinical analysis showed that PRF1 variations were more frequent in relapsing patients and in patients displaying axonal damage. These data suggest that PRF1 variations may influence CIDP development and course.
authors.affiliation: 1] Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy [2] Department of Translational Medicine, Section of Neurology, University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Buttini
authors.affiliation: 1] Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy [2] Department of Health Sciences, University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cappellano
authors.affiliation: Department of Translational Medicine, Section of Neurology, University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ripellino
authors.affiliation: Department of Neurology, University of Padua, Padua, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Briani
authors.affiliation: Department of Neurology, University of Turin, Turin, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Cocito
authors.affiliation: Department of Neurology, University of Milan, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Osio
authors.affiliation: Department of Translational Medicine, Section of Neurology, University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Cantello
authors.affiliation: 1] Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy [2] Department of Health Sciences, University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Dianzani
authors.affiliation: 1] Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy [2] Department of Translational Medicine, Section of Neurology, University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Comi
mesh_terms: D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D054353:Perforin / Q000276:immunology*; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000235:genetics* / Q000276:immunology*
chemical_list: D054353:Perforin