Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: PLCG1

Green List (high evidence)

Comment on list classification: There are now more than 3 unrelated individuals with heterozygous PLCG1 variants and an immune dysregulation disorder, including recurrent infections due to immunological deficiencies. Hence, this gene should be promoted to Green at the next update.

Created: 12 May 2026, 3:01 p.m. | Last Modified: 12 May 2026, 3:01 p.m.

Panel Version: 9.6

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