A Case of IL-7R Deficiency Caused by a Novel Synonymous Mutation and Implications for Mutation Screening in SCID Diagnosis.
Reported synonymous substitutions are generally non-pathogenic, and rare pathogenic synonymous variants may be disregarded unless there is a high index of suspicion. In a case of IL7 receptor deficiency severe combined immunodeficiency (SCID), the relevance of a non-reported synonymous variant was only suspected through the use of additionalin silicocomputational tools, which focused on the impact of mutations on gene splicing. The pathogenic nature of the variant was confirmed using experimental validation of the effect on mRNA splicing and IL7 pathway function. This case reinforces the need to use additional experimental methods to establish the functional impact of specific mutations, in particular for cases such as SCID where prompt diagnosis can greatly impact on diagnosis, treatment, and survival.
Servicio de Inmunología, Hospital Universitario 12 de Octubre , Madrid , Spain.
Fernando
F
Gallego-Bustos
Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH , Rockville, MD , USA.
Valer
V
Gotea
Servicio de Pediatría, Hospital Universitario Clínico , Madrid , Spain.
José T
JT
Ramos-Amador
Unidad de Inmunología, Hospital Universitario La Paz , Madrid , Spain.
Rebeca
R
Rodríguez-Pena
Servicio de Inmunología, Hospital Universitario e Instituto de Investigación Sanitaria Gregorio Marañón , Madrid , Spain.
Juana
J
Gil-Herrera
Servicio de Hematología Oncología, Hospital Universitario La Paz , Madrid , Spain.
Ana
A
Sastre
Instituto de Investigación I+12 , Madrid , Spain.
Aitor
A
Delmiro
GMGF, Aix-Marseille Université, Marseille, France; UMR_S 910, INSERM, Marseille, France.
Ghadi
G
Rai
Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH , Rockville, MD , USA.
Laura
L
Elnitski
Instituto de Investigación I+12, Madrid, Spain; Unidad de Inmunodeficiencias, Pediatría, Hospital Universitario 12 de Octubre, Madrid, Spain.
Luis I
LI
González-Granado
Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain; Instituto de Investigación I+12, Madrid, Spain.
Luis M
LM
Allende
IL-7R; SCID; primary immunodeficiency; splicing; synonymous substitutions