Frontiers in Immunology (Oct 2019)

Novel Compound Heterozygous Mutations in IL-7 Receptor α Gene in a 15-Month-Old Girl Presenting With Thrombocytopenia, Normal T Cell Count and Maternal Engraftment

  • Paola Zangari,
  • Cristina Cifaldi,
  • Silvia Di Cesare,
  • Silvia Di Cesare,
  • Gigliola Di Matteo,
  • Gigliola Di Matteo,
  • Maria Chiriaco,
  • Donato Amodio,
  • Donato Amodio,
  • Nicola Cotugno,
  • Nicola Cotugno,
  • Maia De Luca,
  • Cecilia Surace,
  • Saverio Ladogana,
  • Simone Gardini,
  • Pietro Merli,
  • Mattia Algeri,
  • Paolo Rossi,
  • Paolo Rossi,
  • Paolo Palma,
  • Caterina Cancrini,
  • Caterina Cancrini,
  • Andrea Finocchi,
  • Andrea Finocchi

DOI
https://doi.org/10.3389/fimmu.2019.02471
Journal volume & issue
Vol. 10

Abstract

Read online

Patients with severe combined immunodeficiency (SCID) exhibit T lymphopenia and profound impairments in cellular and humoral immunity. IL-7 receptor α (IL-7Rα) deficiency is a rare form of SCID that usually presents in the first months of life with severe and opportunistic infections, failure to thrive and high risk of mortality unless treated. Here, we reported an atypical and delayed onset of IL7Rα-SCID in a 15-month-old girl presenting with thrombocytopenia. Immunological investigations showed a normal lymphocyte count with isolated CD4-penia, absence of naïve T cells, marked hypergammaglobulinemia, and maternal T cell engraftment. Targeted next generation sequencing (NGS) revealed two novel compound heterozygous mutations in the IL-7Rα gene: c.160T>C (p.S54P) and c.245G>T (p.C82F). The atypical onset and the unusual immunological phenotype expressed by our patient highlights the diagnostic challenge in the field of primary immunodeficiencies (PID) and in particular in SCID patients where prompt diagnosis and therapy greatly affects survival.

Keywords