Combined Immunodeficiency

Gene: DCLRE1C

Green List (high evidence)

RS-SCID
Well-established gene-disease association; over 40 unique DCLRE1C variants have been reported that result in RS-SCID; multiple mouse models

Homozygous and compound heterozygous (missense, in-frame indel, nonsense, frameshift, and large deletion) variants have been reported. *Founder variants c.597C>A p.Tyr199X (Athabascan/ European Origin)

Most individuals presented within the first months of life with oral thrush, diarrhoea, pneumonia, and/or failure to thrive and hypogammaglobulinaemia, absent T and B lymphocytes and increased radiosensitivity.

Omenn Syndrome
1 individual has been reported with DCLRE1C variants resulting in OS phenotype (Another individual from the same family had the same variants as the proband and displayed manifestations consistent with Omenn syndrome; however, they died before a detailed evaluation could be performed)

These individuals were compound heterozygous for missense variants
c.103C>G, p.His35Asp and c.2T>C, p.Met1Thr (1 null and 1 hypomorphic)

The proband presented at 5-months with failure to thrive, generalized lymphadenopathy, erythrodermatitis, alopecia, skin lesions complete absence of B-cell lymphocytes and elevated IgE.

(RS-SCID- Green AND Omenn syndrome -Red)

Created: 19 Aug 2021, 3:18 a.m. | Last Modified: 19 Aug 2021, 3:18 a.m.

Panel Version: 0.345

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Severe combined immunodeficiency, Athabascan type MIM# 602450; Omenn syndrome MIM# 603554

Publications

• 15731174
• 19953608
• 15699179 12055248
• 34220820