Next generation sequencing identifies mutations in Colombian patients with primary immunodeficiency diseases

Autores/as

  • Carlos Andrés Arango-Franco Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Marcela Moncada-Vélez Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Alexander Franco-Gallego Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Lucía Victoria Erazo Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Catalina Martínez Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Sebastián Gutiérrez Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Jesús Armando Álvarez Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Manuela Molina Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Diana Arboleda Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Laura Naranjo Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Juan Álvaro López Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Juan Fernando Alzate Universidad de Antioquia, Centro Nacional de Secuenciación Genómica, Medellin
  • Felipe Cabarcas Universidad de Antioquia, Centro Nacional de Secuenciación Genómica, Medellin
  • Claudia Milena Trujillo-Vargas Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Julio César Orrego Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • Satoshi Okada Hiroshima University Graduate School of Biomedical & Health Sciences, Department of Pediatrics, Hiroshima
  • Anne Puel Institut National de la Santé et de la Recherche Médicale, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Paris
  • Jacinta Bustamante Institut National de la Santé et de la Recherche Médicale, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Paris
  • Jean-Laurent Casanova Institut National de la Santé et de la Recherche Médicale, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Paris
  • Andrés Augusto Arias Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin
  • José Luis Franco Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellin

Palabras clave:

Next generation sequencing, Whole exome sequencing, Primary immunodeficiency diseases

Resumen

Background: The genetic etiology of several primary immunodeficiency diseases (PID) remains elusive. Next generation technologies represent a cost-effective and rapid first-line genetic approach for the evaluation of diseases underlying mendelian traits involved in PID which are characterized by a difficult and late diagnosis.

Methods: In the PID group in Medellin (Colombia), up-today we have performed whole exome sequencing in 93 patients and relatives with severe phenotypes expecting for a gene causing disease underlying a PID.

Results: From 93 WES analysis, gene causing disease have been identified in (n = 15/93) as follows: recurrent infections (n = 4/5, CYBB), BCGitis (n = 1/1, AR IL-12RB1), disseminated infection by Mycobacterium sp. (n = 1/7, AR IL-12RB1), BCGosis, salmonellosis, Mycobacterium tuberculosis and Klebsiella (n = 1, (PR)-IFNGR1), disseminated infection such as candidiasis (n = 5/5, AD- STAT1-GOF), histoplasmosis (n = 1/6, AR NCF4), invasive Corynespora cassiicola infection (n = 1/1, AR CARD9), recurrent infections and glomerulonephritis (n = 1/1, AR C3). Also, we have found several good candidate genes in a cohort of selective IgA deficiency (n = 2/23, PIK3CD, NFKB2), juvenile paracoccidioidomycosis (n = 3/3, IL17RA, IL18R1, PIK3CA) and finally, a cohort with impaired response against pneumococcal vaccines (n = 1/4, NFKBIA). We are performing further analysis in these candidate genes and exome reanalysis in the rest of patients.

Conclusions: We analyzed 93 WES in patients and relatives with several PID phenotypes, we found gene causing defect (n = 15/93) from different cohort of PID patients. WES is emerging as a valuable tool to reach in a timely manner, a PID diagnosis with considerable potential to draw genotype-phenotype correlation.