LETM1, a novel gene encoding a putative EF-hand Ca(2+)-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 (WHS), which is characterized by severe mental and developmental defects. It is thought that haploinsufficiency of more than one gene contributes to the complex phenotype. We have cloned and characterized a novel gene (LETM1) that is deleted in nearly all WHS patients. LETM1 encodes a putative member of the EF-hand family of Ca(2+)-binding proteins. The protein contains two EF-hands, a transmembrane domain, a leucine zipper, and several coiled-coil domains. 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.
Endele
S
S
Children's Hospital, University of Mainz, Mainz, D-55101, Germany.
Fuhry
M
M
Pak
S J
SJ
Zabel
B U
BU
Winterpacht
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics; D020832:EF Hand Motifs / Q000235:genetics*; D005091:Exons; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009468:Neuromuscular Diseases / Q000235:genetics; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013577:Syndrome
D018076:DNA, Complementary