Autoinflammatory disorders

Gene: ELF4

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.

Created: 10 Dec 2025, 2:17 p.m. | Last Modified: 10 Dec 2025, 2:17 p.m.

Panel Version: 2.34

Comment on list classification: As reviewed by Dorota Rowczenio, there is sufficient evidence available for this gene-disease association. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 13 Jun 2025, 3:36 p.m. | Last Modified: 13 Jun 2025, 3:41 p.m.

Panel Version: 2.14

Comment on mode of inheritance: As there are three unrelated female patients reported with heterozygous ELF4 variants and autoinflammatory disorder in PMID:39976696, the MOI has been set as 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)'.

The 'Skewed X-inactivation' tag has also been added as skewed X chromosome inactivation patterns were observed in all three female patients in the same publication.

Created: 13 Jun 2025, 2:33 p.m. | Last Modified: 13 Jun 2025, 3:34 p.m.

Panel Version: 2.11

PMID:34326534 - Two variants identified in three unrelated males with autoinflammatory disease characterised by fever, oral ulcers and mucosal inflammation. Supported by functional studies and mouse model.

PMID:35266071 - Paediatric male patient identified with a hemizygous variant and was suffering from recurrent viral and bacterial respiratory infection, refractory oral ulcer, constipation, and arthritis. Supported by functional studies and mouse model.

PMID:36823308 - Five more male patients presenting mainly with oral ulcer, inflammatory bowel disease-like symptoms, fever of unknown origin, anaemia, or systemic lupus erythematosus.

PMID:38231408 - An international cohort of fourteen patients exhibiting a heterogeneous clinical phenotype including weight loss, oral and gastrointestinal aphthous ulcers, fevers, skin inflammation, gastrointestinal symptoms, arthritis, arthralgia, and myalgia, with findings of increased inflammatory markers, anaemia, neutrophilic leukocytosis, thrombocytosis, intermittently low natural killer and class-switched memory B cells, and increased inflammatory cytokines in the serum.

PMID:38773005 - A 11-year-old boy presented with a Behcet's-like phenotype including elevated inflammatory indicators, ileocecal ulcers and inflammatory cell infiltrations. The patient was treated with long-term immunosuppressant and TNF-alpha blocker. Supporting functional studies available.

PMID:39563044 - Two male patients presented with recurrent oral ulcers and abdominal pain and had significant increase in inflammatory markers, multiple intestinal ulcers, and both patients developed intestinal fistulas.

PMID:39976696 - Three unrelated paediatric female patients, who are all heterozygous for ELF4 variants. Similar to reported male patients, the main clinical features include recurring oral ulcers, abdominal pain and diarrhoea with colonoscopy showing ulcers in the colon. Skewed X chromosome inactivation patterns were observed in all three female patients, with over-inactivation of the X chromosome carrying the wild-type allele confirmed in two of them.

Created: 13 Jun 2025, 2:30 p.m. | Last Modified: 13 Jun 2025, 2:30 p.m.

Panel Version: 2.10

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Autoinflammatory syndrome, familial, X-linked, Behcet-like 2, OMIM:301074

Publications

• 34326534
• 35266071
• 36823308
• 38231408
• 38773005
• 39563044
• 39976696

Green List (high evidence)

Sources: Expert list, Literature

Created: 4 Jun 2025, 4:03 p.m.

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

Phenotypes
Autoinflammatory syndrome, familial, X-linked, Behcet-like 2

Publications

• PMID: 35266071
• PMID: 34326534
• PMID: 39976696
• PMID: 39563044
• PMID: 38773005
• PMID: 38231408
• PMID: 36823308