Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: CD274

Red List (low evidence)

Comment on list classification: Rating Red as only a single family has been reported to date with a biallelic variant (c.682+1G>A) in this gene linked to an autoimmune disorder characterised by neonatal-onset type 1 diabetes mellitus due to complete insulin deficiency (PMID: 38634869)

Created: 17 Oct 2025, 10:09 a.m. | Last Modified: 17 Oct 2025, 10:09 a.m.

Panel Version: 8.53

Red List (low evidence)

In 2 sibs, born of consanguineous Moroccan parents, PMID: 38634869 identified a homozygous splice site mutation in the CD274 gene.

Both presented with neonatal onset of type 1 diabetes mellitus.

The male proband subsequently developed asthma at 5 months of age, autoimmune hypothyroidism at age 3 years, and growth hormone deficiency at age 10. The boy also had mildly impaired intellectual development and speech delay that was attributed to a de novo heterozygous duplication at 7q11.23, which is associated with neurologic phenotypes and growth hormone deficiency. The sister, who did not have this duplication, had no clinical manifestations other than type 1 diabetes
Sources: Literature

Created: 24 Jul 2025, 10:25 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Autoimmune disease, multisystem, infantile-onset, 5

Publications

• PMID: 38634869