Combined Immunodeficiency

Gene: LIG4

Green List (high evidence)

Phenotypes
LIG4; MULTIPLE MYELOMA, RESISTANCE TO

Publications

• 16088910
• 9823897
• 10911993
• 15333585
• 9809069
• 12023982
• 11040211
• 15175260
• 19451691
• 17554302
• 11779494
• 10395545

Green List (high evidence)

2 variants (p.R580Q, p.A842D) in unrelated patients associated with a dominantly inherited
familial immune-dysregulation consisting of autoimmune cytopenias, lymphoproliferation, agammaglobulinemia and adaptive immune cell infiltration into nonlymphoid organ. Reconstitution experiments and
molecular dynamics simulations categorize both missense mutations as loss-of-function and haploinsufficient.

Created: 12 Apr 2023, 10:44 p.m. | Last Modified: 12 Apr 2023, 10:44 p.m.

Panel Version: 1.34

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Combined immune deficiency

Publications

• PMID: 37004747

Green List (high evidence)

12 unrelated individuals displaying combined immunodeficiency with T- and B- Lymphocytopaenia identified with LIG4 variants; 4 of these individuals showed SCID features; two mouse models.

Homozygous and compound heterozygous (Missense & nonsense) variants resulting in truncated protein

Most common phenotype includes microcephaly, developmental and mental delay, T- and B-lymphocytopaenia and varying degrees of hypogammaglobulinaemia.

Created: 3 Aug 2021, 5:35 a.m. | Last Modified: 3 Aug 2021, 5:35 a.m.

Panel Version: 0.251

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
LIG4 syndrome MIM# 606593; T-/B- lymphocytopaenia; Normal NK, radiation sensitivity; Microcephaly; low/ absent B and T cells; low Ig; raised IgM; failure to thrive; bacterial/viral/fungal infections; hypogammaglobulinaemia; neurodevelopmental delay; microcephaly; pancytopaenia

Publications

• 27717373
• 10911993