RT Journal Article
T1 Infantile Encephaloneuromyopathy and Defective Mitochondrial Translation Are Due to a Homozygous RMND1 Mutation
A1 Garcia Diaz, Beatriz
A1 Barros, Mario H.
A1 Sanna, Simone
A1 Emmanuele, Valentina
A1 Akman, Hasan O
A1 Ferreiro Barros, Claudia C.
A1 Horvath, Rita
A1 Tadesse, Saba
A1 El Gharaby, Nader
A1 DiMauro, Salvatore
A1 De Vivo, Darryl C.
A1 Shokr, Aly
A1 Hirado, Michio
A1 Quinzii, Catarina M
K1 Mitocondrias
AB Defects of mitochondrial protein synthesis are clinically and genetically heterogeneous. We previously described a male infant who was born to consanguineous parents and who presented with severe congenital encephalopathy, peripheral neuropathy, myopathy, and lactic acidosis associated with deficiencies of multiple mitochondrial respiratory-chain enzymes and defective mitochondrial translation. In this work, we have characterized four additional affected family members, performed homozygosity mapping, and identified a homozygous splicing mutation in the splice donor site of exon 2 (c.504+1G>A) of RMND1 (required for meiotic nuclear division-1) in the affected individuals. Fibroblasts from affected individuals expressed two aberrant transcripts and had decreased wild-type mRNA and deficiencies of mitochondrial respiratory-chain enzymes. The RMND1 mutation caused haploinsufficiency that was rescued by overexpression of the wild-type transcript in mutant fibroblasts; this overexpression increased the levels and activities of mitochondrial respiratory-chain proteins. Knockdown of RMND1 via shRNA recapitulated the biochemical defect of the mutant fibroblasts, further supporting a loss-of-function pathomechanism in this disease. RMND1 belongs to the sif2 family, an evolutionary conserved group of proteins that share the DUF155 domain, have unknown function, and have never been associated with human disease. We documented that the protein localizes to mitochondria in mammalian and yeast cells. Further studies are necessary for understanding the function of this protein in mitochondrial protein translation.
PB The American Society of Human Genetics
YR 2012
FD 2012
LK https://hdl.handle.net/10630/32336
UL https://hdl.handle.net/10630/32336
LA eng
NO Garcia-Diaz B, Barros MH, Sanna-Cherchi S, Emmanuele V, Akman HO, Ferreiro-Barros CC, Horvath R, Tadesse S, El Gharaby N, DiMauro S, De Vivo DC, Shokr A, Hirano M, Quinzii CM. Infantile encephaloneuromyopathy and defective mitochondrial translation are due to a homozygous RMND1 mutation. Am J Hum Genet. 2012 Oct 5;91(4):729-36. doi: 10.1016/j.ajhg.2012.08.019.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026