List of 9 pathogenic variants identified in genes implicated in IEIs with their associated phenotypic classification as outlined in 2022 by the International Union of Immunological Societies,1 coding DNA reference sequence, protein-level amino acid sequences (if applicable), gene transcript, and variant-specific references denoted by PubMed Identifier
| IUIS phenotypic classification . | Gene . | cDNA (protein) . | Transcript . | Zygosity . | Disease . | Inheritance . | PMID . |
|---|---|---|---|---|---|---|---|
| Autoinflammatory disorders | MVK | c.1129G>A (p.Val377Ile) | NM_000433.3 | Het | Mevalonate kinase deficiency (hyper-IgD syndrome) | AR | 10369261 |
| Diseases of immune dysregulation | PRF1 | c.853_855del (p.Lys285del) | NM_001083116.1 | Het | Perforin deficiency | AR | |
| Combined immunodeficiencies with associated or syndromic features | PMS2 | c.746_753del (p.Asp249Valfs∗2) | NM_000535.5 | Het | PMS2 deficiency | AR | 20487569 and 27435373 |
| RMRP | n.239C>T | NR_003051.3 | Het | Cartilage hair hypoplasia | AR | 11940090 | |
| WAS | c.1203del (p.Pro402Argfs∗43) | NM000377.2 | Het (female) | Wiskott-Aldrich Syndrome | XL | ||
| Predominantly antibody deficiencies | TNFRSF13B | c.542C>A (p.Ala181Glu) | NM_012452.2 | Het | TACI deficiency | AR | 16007086; 16007087; and 20156508 |
| Congenital defects of phagocyte number or function | CFTR (2) | c.2052del (p.Lys684Asnfs∗38) | NM_000492.3 | Het | Cystic fibrosis | AR | 23974870 |
| c.1521_1523del (p.Phe508del) | Het | 2475911; 15371902; and 23974870 | |||||
| Bone marrow failure | FANCL | c.296_297del (p.Gln99Argfs∗17) | NM_018062.3 | Het | Fanconi anemia type L | AR |
| IUIS phenotypic classification . | Gene . | cDNA (protein) . | Transcript . | Zygosity . | Disease . | Inheritance . | PMID . |
|---|---|---|---|---|---|---|---|
| Autoinflammatory disorders | MVK | c.1129G>A (p.Val377Ile) | NM_000433.3 | Het | Mevalonate kinase deficiency (hyper-IgD syndrome) | AR | 10369261 |
| Diseases of immune dysregulation | PRF1 | c.853_855del (p.Lys285del) | NM_001083116.1 | Het | Perforin deficiency | AR | |
| Combined immunodeficiencies with associated or syndromic features | PMS2 | c.746_753del (p.Asp249Valfs∗2) | NM_000535.5 | Het | PMS2 deficiency | AR | 20487569 and 27435373 |
| RMRP | n.239C>T | NR_003051.3 | Het | Cartilage hair hypoplasia | AR | 11940090 | |
| WAS | c.1203del (p.Pro402Argfs∗43) | NM000377.2 | Het (female) | Wiskott-Aldrich Syndrome | XL | ||
| Predominantly antibody deficiencies | TNFRSF13B | c.542C>A (p.Ala181Glu) | NM_012452.2 | Het | TACI deficiency | AR | 16007086; 16007087; and 20156508 |
| Congenital defects of phagocyte number or function | CFTR (2) | c.2052del (p.Lys684Asnfs∗38) | NM_000492.3 | Het | Cystic fibrosis | AR | 23974870 |
| c.1521_1523del (p.Phe508del) | Het | 2475911; 15371902; and 23974870 | |||||
| Bone marrow failure | FANCL | c.296_297del (p.Gln99Argfs∗17) | NM_018062.3 | Het | Fanconi anemia type L | AR |
All variants in the heterozygous state are not associated with disease. One patient harbored 2 different pathogenic variants in IEI genes (CFTR and FANCL).
AR, autosomal recessive; cDNA, coding DNA reference sequence; Het, heterozygous; IgD, immunoglobulin D; IUIS, International Union of Immunological Societies; PMID, PubMed Identifier; XL, X-linked.