LEMD3 gene

The LEMD3 gene (LEMD3 stands for: LEM Domain Containing 3) encodes the inner nuclear membrane protein Man1, which is localized to chromosome 12q14.3. The encoded protein antagonizes TGF-beta induced cell proliferation arrest. Furthermore, the encoded protein may act as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with R-SMAD proteins.

Two transcript variants encoding different isoforms were found for the LEMD3 gene. Mutations in this gene have been associated with

• Buschke-Ollendorff syndrome

and

• Melorheostosis associated with osteopoikilosis.

Of note in a familial LEMD3 mutation is the case description of osteopoikilosis associated with late-onset localized morphea-type scleroderma (Korman B et al. 2016). DNA sequencing of this case revealed a previously undescribed nonsense mutation (Trp621X) in the LEMD3 gene encoding Man1.

1. Korman B et al. (2016) Mutation in LEMD3 (Man1) Associated with Osteopoikilosis and Late-Onset Generalized Morphea: A New Buschke-Ollendorf Syndrome Variant. Case Rep Dermatol Med. 2016:2483041.