Ectodermal Dysplasia

Gene: LEF1

Green List (high evidence)

Monoallelic variants in LEF1 reported in 11 affected individuals from 4 unrelated families, and a biallelic variant reported in an affected individual from a consanguineous family. The phenotypic spectrum included various limb malformations, such as radial ray defects, polydactyly or split hand/foot, and ectodermal dysplasia. Haploinsufficiency or loss of DNA binding postulated to be responsible for a mild to moderate phenotype, whereas loss of β-catenin binding caused by biallelic variants postulated to be associated with a severe phenotype.

Created: 1 Sep 2022, 6:22 a.m. | Last Modified: 1 Sep 2022, 6:22 a.m.

Panel Version: 0.68

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Syndromic disease, MONDO:0002254, LEF1-related

Publications

• 32022899
• 35583550

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. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human.
Sources: Literature

Created: 4 Jun 2020, 12:36 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Ectodermal dysplasia, no OMIM# yet

Publications

• PMID: 32022899