The effect of mutatio-type on proteo-phenotype and clinico-phenotype in selected primary immunodeficiencies.

Halacli S.

Immunologic research, vol.70, no.1, pp.56-66, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 70 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1007/s12026-021-09239-8
  • Journal Name: Immunologic research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.56-66
  • Keywords: Primary immunodeficiency, Inheritance, Mutation type, Protein domain, Protein expression level, Protein functions, Clinical severity, HYPER-IGM SYNDROME, COMBINED IMMUNE-DEFICIENCY, CD40 LIGAND EXPRESSION, JAK3 GENE, DIAGNOSIS, FAMILY
  • Hacettepe University Affiliated: Yes


In the diagnosis of primary immunodeficiencies which are heterogeneous groups of genetic disorders, next-generation sequencing strategies take an important place. Protein expression analyses and some functional studies which are fundamental to determine the pathogenicity of the mutation are also performed to accelerate the diagnosis of PIDs before sequencing. However, protein expressions and functions do not always reflect the genetic and clinical background of the disease even the existence of a pathogenic variant or vice versa. In this study, it was aimed to understand genotype-proteophenotype-clinicophenotype correlation by investigating the effect of mutation types on protein expression, function, and clinical severity in X-linked, autosomal dominant, and autosomal recessive forms of PIDs. It was searched in PubMed and Web of Science without any restrictions on study design and publication time. Totally, 1178 patients with PIDs who have 553 different mutations were investigated from 174 eligible full-text articles. For all mutations, the effect of mutation type on protein expressions and protein functions was analyzed. Furthermore, the most frequent missense and nonsense mutations that were identified in patients with PIDs were evaluated to determine the genotype-clinicophenotype correlation. Protein expressions and functions were changed depending on the mutation type and the affected domain. A significant relationship was observed between protein expression level and clinical severity among all investigated patients. There was also a positive correlation between clinical severity and the affected domains. Mutation types and affected domains should be carefully evaluated with respect to protein expression levels and functional changes during the evaluation of clinico-phenotype.