Autoinflammatory disorders

Gene: PLCG1

Green List (high evidence)

Comment on list classification: There are now 3 unrelated individuals with heterozygous PLCG1 variants and an immune dysregulation disorder, including variable autoimmune feature. Hence, this gene should be promoted to Green at the next update.

Created: 12 May 2026, 3:06 p.m. | Last Modified: 12 May 2026, 3:06 p.m.

Panel Version: 3.5

PMID: 40862571 Ma et al., 2025 (based on pre-print mentioned in previous reviews)
Report of seven individuals from 4 unrelated families with heterozygous missense variants in PLCG1: 3 individuals with de novo het variants: c.3056A>G, p.(Asp1019Gly)], [c.1139A>G, p.(His380Arg)] and [c.3494A>G, p.(Asp1165Gly)]. Individuals 4–7 are from the same family, and all carry the PLCG1 variant [c.1789C>T p.(Leu597Phe)].
Phenotypic spectrum: hearing loss (5/7, mild to profound), cardiac septal defects (3/6), and other less specific syndromic findings. Abnormal brain MRI findings in 2/3 assessed. Various immunological issues included:
P3: T lymphocytopenia, recurrent pulmonary infections;
P4: joint inflammation, tarsal synovitis, recurrent respiratory and lung infections, as well as inflammatory lymphadenopathy;
P5: immune thrombocytopenic purpura, polyarthritis, autoimmune pulmonary fibrosis, pneumococcal sepsis with chronic thrombocytopenia and IgA and IgG2 deficiency;
P6: history of recurrent upper respiratory and lung infections due to a mild IgA and IgG2 deficiency;

PMID: 37422272 Tao et al., 2024
7yo female patient with a de novo p.S1021F variant in PLCG1 and early-onset immune dysregulation disease: recurrent skin ecchymosis, epistaxis and gingival bleeding, lymphadenopathy. No mention of hearing loss.
Sources: Literature

Created: 12 May 2026, 2:59 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
?Immune dysregulation, autoimmunity, and autoinflammation, OMIM:620514; immune dysregulation, autoimmunity, and autoinflammation, MONDO:0957790

Publications

• 37422272
• 40862571