title: LETM1, a gene deleted in Wolf-Hirschhorn syndrome, encodes an evolutionarily conserved mitochondrial protein.
abstract: 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. LETM1 is deleted in almost all patients with the full phenotype and has recently been suggested as an excellent candidate gene for the seizures in WHS patients. We have shown that LETM1 is evolutionarily conserved throughout the eukaryotic kingdom and exhibits homology to MDM38, a putative yeast protein involved in mitochondrial morphology. Using LETM1-EGFP fusion constructs and an anti-rat LetM1 polyclonal antibody we have demonstrated that LETM1 is located in the mitochondria. The present study presents information about a possible function for LETM1 and suggests that at least some (neuromuscular) features of WHS may be caused by mitochondrial dysfunction.
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 10, D-91054 Erlangen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schlickum
authors.forename: Abhay
authors.initials: A
authors.lastname: Moghekar
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Simpson
authors.forename: Cordula
authors.initials: C
authors.lastname: Steglich
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Brien
authors.forename: Andreas
authors.initials: A
authors.lastname: Winterpacht
authors.forename: Sabine U
authors.initials: SU
authors.lastname: Endele
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics; D030562:Databases, Protein; D019143:Evolution, Molecular; D017353:Gene Deletion; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000235:genetics; D024101:Mitochondrial Proteins / Q000032:analysis* / Q000235:genetics*; D051381:Rats; D012640:Seizures / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013577:Syndrome
chemical_list: D002135:Calcium-Binding Proteins; C488528:LETM1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins