Retinal disorders

Gene: AIRE

Green List (high evidence)

Comment on list mode of inheritance: Autoimmune polyendocrinopathy syndrome type I (APS-1) is characterised primarily by the presence of hypoparathyroidism, adrenal insufficiency, chronic mucocutaneous candidiasis, and enamel hypoplasia. There are at least 7 unrelated individuals with biallelic variants in AIRE, reported to have retinopathy as an additional APS-1 disease presentation. Monoallelic variants in AIRE have not been linked to retinopathy. Based on the available evidence, the MOI should be changed to BIALLELIC, autosomal or pseudoautosomal.

Created: 5 Nov 2025, 3:18 p.m. | Last Modified: 5 Nov 2025, 3:20 p.m.

Panel Version: 8.61

MONOALLELIC:
PMID: 37235056 Oftedal et al., 2023
11 unrelated patients with heterozygous AIRE mutations. Affected individuals presented with: Enteropathy, gastritis, UC (5/11), vitiligo (2/11), immunodeficiency (2/11), pernicious anemia (2/11). Some variants did not segregate with disease in the families - incomplete penetrance suggested. No ocular phenotype reported in the cohort.

BIALLELIC:
PMID: 25926518 Borgault et al., 2015
Report of 5 molecularly confirmed cases with APS1 known to have ocular involvement (age range: 19 months–44 years). All patients showed fundus changes ranging from isolated patchy atrophy of the RPE to an RP-like fundus and attenuated vasculature.
P1: female, P539L/P539L - systemic findings: Mucocutaneous candidiasis, Hypoparathyroidism, Alopecia, Growth retardation.
P2: male, R257X/c.967_c.979del13 - systemic findings: Mucocutaneous candidiasis, Hypoparathyroidism, Acne
P3: female, c.967_c.979del13/c.967_c.979del13 - systemic findings: Mucocutaneous candidiasis, Hypoparathyoidism, Adrenal insufficiency, Osteopenia, Vitiligo, Sicca syndrome, Multiple bacterial/fungal infections
P4: male, R256X/c.967_c.979del13 - systemic findings: Oesophageal candidiasis/stricture, Hypoparathyroidism, Hypogonadism, Nails dystrophy, Alopecia
P5: female, c.463G>A/p.G155S/p.G155S - systemic findings: Autoimmune hepatitis, Mucocutaneous candidiasis, Hypoparathyroidism, Addison disease

PMID: 34122451 Sakaguchi et al. 2021
2-year-old Japanese girl homozygous for c.415C>T, (p.Arg139Ter), with bilateral autoimmune retinopathy, anti-recoverin antibodies, and steroid-responsive acute liver failure.

PMID: 37711606 Wang et al., 2023
3-year-old Chinese boy - F1-II2 - homozygous for c.769C>T, (p.Arg257Ter) - widespread tapetoretinal degeneration without bone-spicule pigmentation. rod and cone responses were non-recordable on ERG recordings. No other systemic symptoms.

AIRE is linked to AR & AD Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia, 240300 (OMIM, accessed 5th Nov 2025).

Created: 5 Nov 2025, 3:13 p.m. | Last Modified: 5 Nov 2025, 3:24 p.m.

Panel Version: 8.63

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia, OMIM:240300; autoimmune polyendocrine syndrome type 1, MONDO:0009411

Publications

• 25926518
• 34122451
• 37711606
• 37235056

Green List (high evidence)

AIRE rated as Green as has a relevant phenotype to be included on the panel following discussion in Genomics England Clinical Team Meeting, 7th October 2019.

Created: 7 Oct 2019, 4:22 p.m. | Last Modified: 7 Oct 2019, 4:22 p.m.

Panel Version: 1.191

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia, 240300

Green List (high evidence)