The study has been approved by ESID.
Proposed by: Salome Stein and Mike Recher, University Hospital Basel, Switzerland
Dear colleagues,
We would like to invite you to participate in an ESID-supported study on monoallelic LIG4-dependent combined immunodeficiency.
Combined immunodeficiency (CID) due to biallelic LIG4 mutations is rare but well established. We recently published four patients from three non-related families manifesting with CID associated with novel monoallelic LIG4 mutations via haploinsufficiency (Jauch et al., J Allergy Clin Immunol, 2023, PMID: 37004747). These patients had variable infection susceptibility, lymphoproliferation and autoimmunity, displayed antibody deficiency ranging from mild to agammaglobulinemia, low naive T cells, and low Vα7.2+ T cells – features very similar to classical recessive bi-allelic LIG4-IEI. In one family, monoallelic LIG4 mutation carriage and immune-dysregulation segregated as an autosomal dominant trait. The extended clinical phenotype, penetrance, involved LIG4 variants and molecular mechanisms underlying LIG4 insufficiency remain only partly understood.
We are collecting clinical and genetic information on patients with:
- Rare monoallelic LIG4 mutations (population frequency <1% based on gnomAD)
- Predicted functional relevance (CADD score >15)
- Any age
- Explicitly including parents and siblings of children with bi-allelic LIG4-dependent CID (carriage of monoallelic LIG4 mutation should have been confirmed)
If your centre follows patients with monoallelic LIG4 variants and you are interested in participating, please contact: salome.stein@unibas.ch and cc: mike.recher@usb.ch. A case report form will be provided upon expression of interest.
All data will be handled confidentially.
