LETM1, a novel gene encoding a putative EF-hand Ca2+-binding protein, flanks the Wolf-Hirschhorn syndrome (WHS) critical region and is deleted in most WHS patients

Deletions within human chromosome 4p16.3 cause Wolf-Hirschhorn syndrome (WH S), which is characterized by severe mental and developmental defects. It i s thought that haploinsufficiency of more than one gene contributes to the complex phenotype. We have cloned and characterized a novel gene (LETM1) th at is deleted in nearly all WHS patients. LETM1 encodes a putative member o f the EF-hand family of Ca2+-binding proteins. The protein contains two EF- hands, a transmembrane domain, a leucine zipper, and several coiled-coil do mains. On the basis of its possible Ca2+-binding property and involvement i n Ca2+ signaling and/or homeostasis, we propose that haploinsufficiency of LETM1 may contribute to the neuromuscular features of WHS patients, (C) 199 9 Academic Press.