title: Analyses of the PRF1 gene in individuals with hemophagocytic lymphohystiocytosis reveal the common haplotype R54C/A91V in Colombian unrelated families associated with late onset disease.
abstract: Familial hemophagocytic lymphohistiocytosis (FHL), is a rare autosomal recessive disorder characterized by an impairment of cytotoxic cells and uncontrolled activation of macrophages. This study presents the first description of four patients with FHL type 2 in Latin America. Patient 1 fulfilled the disease diagnostic criteria since 2 months of age, whereas patients 2, 3 and 4 exhibited the typical manifestations of the disease only later in their childhood. The PRF1 genetic analysis in these patients revealed two previously reported mutations: L17fsx50 and R54C. Interestingly, seven out of the 8 alleles evaluated here in patients carried the haplotype R54C/A91V, suggesting that this is a highly frequent FHL type 2 allele in Colombia. This haplotype confers residual cytotoxic function leading to late onset disease. Therefore, this report highlights the remarkable complexity of FHL diagnostic, emphasizing the importance of the genetic characterization of the disease.
authors.affiliation: Group of Primary Immunodeficiencies, University of Antioquia, Calle 62 #52-59 Lab.530, Medellín, Colombia. isapisan@yahoo.com
authors.forename: Isaura P
authors.initials: IP
authors.lastname: Sánchez
authors.forename: Lucía C
authors.initials: LC
authors.lastname: Leal-Esteban
authors.forename: Jesús A
authors.initials: JA
authors.lastname: Álvarez-Álvarez
authors.forename: Camilo A
authors.initials: CA
authors.lastname: Pérez-Romero
authors.forename: Julio C
authors.initials: JC
authors.lastname: Orrego
authors.forename: Malyive L
authors.initials: ML
authors.lastname: Serna
authors.forename: Yadira
authors.initials: Y
authors.lastname: Coll
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Caicedo
authors.forename: Edwin
authors.initials: E
authors.lastname: Pardo-Díaz
authors.forename: Jacques
authors.initials: J
authors.lastname: Zimmer
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Bleesing
authors.forename: José L
authors.initials: JL
authors.lastname: Franco
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Trujillo-Vargas
mesh_terms: D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003105:Colombia; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin