Biallelic variant in LEF1 are associated with a new syndrome combining ectodermal dysplasia and limb malformations through altered WNT signalling

We found a homozygous duplication of three base pairs in LEF1 (c.69_71dupGAT; p.M23_I24insM) in patient manifesting ectrodactyly ectrodermal dysplasia syndrome without cleft lip/palate. We aim to elucidate the consequences of this homozygous LEF1 varinat on transcriptome profiling of the patient compared to age matched control. Collectively, we observed differential expression of genes involved in the the canonical WNT pathway. Interestingly, 30 out of 39 known HOX genes were significantly differentially expressed. We concluded that the identified LEF1 variant disturb the canonical WNT signaling pathway.