Ectodermal dysplasia

Gene: LEF1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 6 Dec 2024, 12:48 p.m. | Last Modified: 6 Dec 2024, 12:48 p.m.

Panel Version: 3.35

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on phenotypes: This gene has been associated with relevant phenotypes in OMIM (MIM #621224) and the OMIM record was last accessed on 18 December 2025.

Created: 18 Dec 2025, 9:48 p.m. | Last Modified: 18 Dec 2025, 9:48 p.m.

Panel Version: 4.20

Comment on list classification: There are four unrelated families reported with monoallelic variants and a single individual reported with biallelic variants. Hence, this gene should be promoted to green rating in the next GMS review and the MOI should be set as 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'.

Created: 24 Jan 2024, 10:36 p.m. | Last Modified: 24 Jan 2024, 10:40 p.m.

Panel Version: 3.28

Comment on phenotypes: Germline variants in this gene have not yet been associated with any phenotypes in OMIM, but monoallelic variants have been associated with LEF1-related ectodermal dysplasia and limb malformation in Gene2Phenotype ('moderate' rating on the DD panel).

Created: 24 Jan 2024, 10:33 p.m. | Last Modified: 24 Jan 2024, 10:33 p.m.

Panel Version: 3.26

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
ectodermal dysplasia syndrome, MONDO:0019287; limb malformations

Publications

• 35583550

Green List (high evidence)

Monoallelic variants in LEF1 were detected in 11 affected individuals from 4 unrelated families, and a biallelic variant was detected in an affected individual from a consanguineous family. The phenotypic spectrum includes various limb malformations, such as radial ray defects, polydactyly or split hand/foot, and ectodermal dysplasia. Functional study showed that haploinsufficiency or loss of DNA binding are responsible for a mild to moderate phenotype, whereas loss of β-catenin binding caused by biallelic variants is associated with a severe phenotype.

Created: 30 Nov 2022, 7:01 p.m. | Last Modified: 30 Nov 2022, 7:01 p.m.

Panel Version: 2.1

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Radial ray defects; polydactyly; split hand/foot; ectodermal dysplasia

Publications

• 35583550

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Levy et al. 2020 (PMID: 32022899) report 2 patients with signs of ectodermal dysplasia harbouring de novo deletions that overlap only at the regions containing LEF1. Supportive mouse model. Rating Red as currently there is no evidence of SNVs in LEF1 relating to this phenotype.

Created: 30 Jun 2021, 1:58 p.m. | Last Modified: 30 Jun 2021, 1:58 p.m.

Panel Version: 1.20

Red List (low evidence)

In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. One report of two unrelated patients with 4q25 de novo deletion encompassing LEF1 , associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. No reports of SNVs.
Sources: Literature

Created: 9 Jun 2020, 10:24 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Ectodermal dysplasia, no OMIM# yet

Publications

• 32022899