Combined Immunodeficiency

Gene: LCK

Green List (high evidence)

Description of a second unrelated patient with novel biallelic missense LCK c.1393T>C, p.C465R variant in a patient from
a consanguineous Syrian family with profound T-cell immune deficiency characterized by complete LCK protein expression deficiency and ensuing proximal TCR signaling-and CD4 and CD8-co-receptor-mediated functional and phenotypical defects.
PMID: 27087313 reported 3 siblings of a consanguineous family presenting with recurrent pneumonia and severe viral skin disease leading to malignant transformation. The patients had an intronic LCK c.188-2A>G splice site variant resulting in skipping of exon 3 and mRNA decay. Clinical data alongside with CD4+ T-cell lymphocytopenia suggested a hypomorphic
LCK deficiency.

Created: 18 Dec 2023, 11:52 p.m. | Last Modified: 18 Dec 2023, 11:52 p.m.

Panel Version: 1.54

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined Immune deficiency

Publications

• PMID: 38100037
• PMID: 27087313

I don't know

Only 1 individual with a LCK variant identified with associated CID phenotype caused by LCK-deficiency had been reported; homozygous missense variant (p.L341P) altering a highly conserved residue in the kinase domain.

Multiple LCK-deficient mice models demonstrating pronounced thymic atrophy and dramatic loss of double positive (CD4+/CD8+) cells, consistent with Immunodeficiency 22 phenotype.

Patient displayed features early in life consisting of failure to thrive, diarrhoea, recurrent respiratory infections and immunological profile of CD4+ T-cell Lymphopaenia, low expression levels of CD4/CD8 cells.

Created: 27 Jul 2021, 3:19 a.m. | Last Modified: 27 Jul 2021, 3:19 a.m.

Panel Version: 0.232

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency 22 MIM# 615758; Recurrent infections; Immune dysregulation; autoimmunity; Low CD4+; low CD8+; restricted T cell repertoire; poor TCR signaling; Normal IgG/IgA; high IgM; failure to thrive; diarrhoea; lymphopenia; hypogammaglobulinemia; anaemia; thrombocytopaenia; CD4+ T-cell lymphopenia

Publications

• 22985903
• 1579166
• 11021796