Evaluation of genetic mutations in severe combined immunodeficiency (scid) patients

Zahra Shahbazi,1 Reza mahdian,2,* Asghar aghamohammadi,3 Morteza karimipour,4 Shirin shahbazi,5 Mohammad hamid,6

1. pasteur institute of Iran
2. pasteur institute of Iran
3. Tehran University of Medical Science School of Medicine Department of Pediatrics .Division of Clinical Immunology and
4. pasteur institute of Iran
5. Tarbiat modares university- Faculty of medical scie nces – Medical genetics depertment
6. pasteur institute of iran



Severe combined immunodeficiencies (scids) are a group of inherited disorders that are responsible for severe dysfunctions of the immune system. the estimate of the incidence of scid was one in 50,000 to 100,000. scid classes are: cell (t−b+nk+) (t−b+nk−)(t−b−nk+)(t−b−nk−). in this study we tried to find causing genetic mutations in iranian scid patient. first we focused on 7 frequent genes, and if we did not find the causing mutation, we used whole exome sequencing (wes) method.


This study was carried out on 33 scid patients being referred to children’s medical center, tehran university of medical sciences. this study was approved by ethics committee of pasteur institute of iran. early advanced immunological screening was investigated: cbc , immunoglobulin (igg, iga, igm and ige) levels, flow cytometry (cd3, cd4, cd8, cd19 and cd16/56). genetic studies were performed by sanger sequencing of all exons and exon/intron junctions of (rag1/rag2), (il-7ra), (ada/pnp), (jak3/il2rg) genes. whole exome sequencing (wes) was the next step for mutation analysis.


We report here the results for the patients of (t- b- nk+) and (t- b+ nk+), categories. (t- b- nk+): seven patients with mutations in rag1 gene (6 missense,1 nonsense) and two patients with mutations in rag2 gene(missense). (t- b+ nk+): none of the patients that were candidate for il7ra mutation analysis, have mutation in this gene. wes results shows: one patient with nonsense mutation in cd3e gene, one patient with nonsense mutation in cd3d gene, one patient with missense mutation in cd27 gene, three patient with missense mutation in artemis gene (1 nonsense, 1missense,1 frame shift deletion), one patient with missense mutations in ciita gene (in frame deletion) other patients were studied in two other phenotypic categories, the results do not report in this abstract.


Our study confirms that il7ra gene may not be the right and suitable first candidate gene for mutation analysis in (t- b+ nk+) phenotypic group and perhaps other genes of this group (for example cd3 genes) can be the first line of mutation detection studies in iran.


Wes, wgs, scid