Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: LRRC32

Comment on list classification: Novel candidate gene added by Boaz Palterer. Rating Red as currently there is not enough evidence to support this gene-disease association.

Lehmkuhl et al. 2021 (PMID: 34059789) - 2 unrelated patients with immunodeficiency were found to harbour two rare heterozygous missense variants each in the LRRC32 gene (p.Arg312Cys (recurring), p.Trp247Ter, p.Arg421Gln) - variants were in cis in one patient, but in trans in the other.

Note that a different homozygous founder variant was also found in 2 families with GDD, cleft palate, and proliferative retinopathy (PMID: 30976112) - none of these features were evident in the two cases discussed here.

Created: 9 Jun 2021, 1:24 p.m. | Last Modified: 9 Jun 2021, 1:24 p.m.

Panel Version: 2.426

Red List (low evidence)

Lehmkuhl et al. described two patients with immune dysregulation and mutations of LRRC32. Both patients carried two rare variants, however, patient 1 has both variants in cis, while patient 2 was a compound heterozygote. Reduced protein expression ex-vivo was demonstrated. Conditional mice KO model recapitulated the phenotype.
Sources: Literature

Created: 7 Jun 2021, 11:33 p.m.

Mode of inheritance
Unknown

Phenotypes
Common variable immunodeficiency; Enteropathy; Lymphopenia; Reduced Tregs

Publications

• 34059789