Combined Immunodeficiency

Gene: CD40LG

Green List (high evidence)

Well-established gene-disease association; more than 20 unrelated individuals and multiple CD40LG deficient mouse models demonstrate an association with X-linked recessive hyper IgM syndrome.
Heterozygous females are characteristically asymptomatic (normal immunoglobulin levels); however, there have been rare cases of affected females expressing clinical phenotypes due to skewed X-chromosome inactivation (PMID: 16311023 & 9933119)

Variants identified include missense, in-frame indel, nonsense, frameshift, large deletion and complex rearrangements resulting in LOF.

Typical immunological profile includes decreased IgG/IgA/IgE levels with normal-increased IgM levels, resulting in susceptibility to severe and opportunistic viral/bacterial infections.

Created: 22 Jul 2021, 1:44 a.m. | Last Modified: 26 Aug 2021, 4:32 a.m.

Panel Version: 0.381

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Immunodeficiency, X-linked, with hyper-IgM MIM# 308230; Severe opportunistic infections (recurrent), idiopathic neutropaenia; dysgammaglobulinaemia hepatitis; cholangitis; cholangiocarcinoma; autoimmune blood cytopenias; haemolytic anaemia; thrombocytopaenia; diarrhoea; peripheral neuroectodermal tumours

Publications

• 7679801
• 7679206
• 8094231
• 9933119
• 15358621
• 15997875
• 7678782
• 7915248
• 15367912
• 7518839
• 16311023
• 9933119
• 12402041
• 7882172
• 33475257