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
| Autor: | Lucía Carolina Leal-Esteban, Jack J. Bleesing, Yadira Coll, Yolanda Caicedo, Claudia M. Trujillo-Vargas, José Luis Franco, Isaura Pilar Sánchez, Julio César Orrego, Jacques Zimmer, Jesús A. Álvarez-Álvarez, Malyive L. Serna, Camilo A. Perez-Romero, Edwin Pardo-Díaz |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Pore Forming Cytotoxic Proteins medicine.medical_specialty Immunology Disease Colombia Genetic analysis Lymphohistiocytosis Hemophagocytic Medical microbiology medicine Humans Immunology and Allergy Genetic Predisposition to Disease Age of Onset Allele Child Gene Genetics biology Perforin Haplotype Infant Membrane Proteins Familial Hemophagocytic Lymphohistiocytosis Killer Cells Natural Haplotypes Child Preschool Mutation biology.protein Female |
| Zdroj: | Journal of Clinical Immunology. 32:670-680 |
| ISSN: | 1573-2592 0271-9142 |
| DOI: | 10.1007/s10875-012-9680-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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