Disease relevance of LETM1

• The leucine zipper-, EF-hand-containing transmembrane protein 1 (LETM1) has recently been cloned in an attempt to identify genes deleted in Wolf-Hirschhorn syndrome (WHS), a microdeletion syndrome characterized by severe growth and mental retardation, hypotonia, seizures, and typical facial dysmorphic features [1].
• OBJECTIVE: We investigated whether neuromyelitis optica (NMO) IgG seropositivity at the initial presentation of longitudinally extensive transverse myelitis (LETM) predicts relapse of myelitis or development of optic neuritis [2].

High impact information on LETM1

• Among the candidate genes already described for WHS, LETM1 (leucine zipper/EF-hand-containing transmembrane) is likely to be pathogenetically involved in seizures [3].
• This mutant phenotype is complemented by the expression of the human LETM1 gene in yeast, indicating a functional conservation of LetM1/Yol027 proteins from yeast to man [4].
• The LETM1/YOL027 gene family encodes a factor of the mitochondrial K+ homeostasis with a potential role in the Wolf-Hirschhorn syndrome [4].
• Using LETM1-EGFP fusion constructs and an anti-rat LetM1 polyclonal antibody we have demonstrated that LETM1 is located in the mitochondria [1].
• LETM1 encodes a putative member of the EF-hand family of Ca(2+)-binding proteins [5].

Anatomical context of LETM1

• Thus, YOL027/LETM1 are the first genes shown to encode factors involved in both K+ homeostasis and organelle volume control [4].
• Electroneutral K+/H+ exchange in mitochondrial membrane vesicles involves Yol027/Letm1 proteins [6].

Associations of LETM1 with chemical compounds

• On the basis of its possible Ca(2+)-binding property and involvement in Ca(2+) signaling and/or homeostasis, we propose that haploinsufficiency of LETM1 may contribute to the neuromuscular features of WHS patients [5].

Regulatory relationships of LETM1

• LETM1 was co-precipitated with BCS1L and formation of the LETM1 complex depended on BCS1L levels, suggesting that BCS1L stimulates the assembly of the LETM1 complex [7].

Other interactions of LETM1

• The deletion encompasses 191.5 kb and includes WHSC2, but not LETM1 [8].
• Thus, manifestations attributable to this deletion are reduced weight for height, minor facial anomalies, ADHD and some learning and fine motor deficiencies, while seizures may be associated with deletions of LETM1 [8].

References