Monogenic hearing loss

Gene: PLCG1

Green List (high evidence)

Comment on list classification: There are now 3 unrelated individuals with heterozygous PLCG1 variants and hearing loss. Hence, this gene should be promoted to Green at the next update.

Created: 26 May 2026, 10:28 a.m. | Last Modified: 26 May 2026, 10:28 a.m.

Panel Version: 6.13

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.

Created: 12 May 2026, 2:53 p.m. | Last Modified: 12 May 2026, 2:53 p.m.

Panel Version: 6.7

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
?Immune dysregulation, autoimmunity, and autoinflammation, OMIM:620514

Publications

• 37422272
• 40862571

I don't know

If PMID: 38260438 is accepted for publication, a green recommendation for PLCG1 would be made.

Created: 11 Nov 2024, 3:47 p.m. | Last Modified: 11 Nov 2024, 3:47 p.m.

Panel Version: 4.60

If the preprint PMID: 38260438 is accepted for publication, a green recommendation would be made for PLCG1.

Created: 11 Nov 2024, 3:44 p.m. | Last Modified: 11 Nov 2024, 3:44 p.m.

Panel Version: 4.60

I don't know

Limited case info in preprint, but PMID: 38260438 (2024) reported three unrelated individuals with de novo heterozygous missense variants in PLCG1, with symptoms including deafness, ophthalmologic abnormalities, cardiac septal defects, abnormal brain MRI and immune defects
Sources: Literature

Created: 18 Oct 2024, 10:29 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
hearing impairment; ophthalmologic abnormalities; cardiac septal defects

Publications

• PMID: 38260438