title: Hearing impairment and renal failure associated with RMND1 mutations.
abstract: Recently, two research groups reported that mutations in RMND1 were associated with encephalopathy, elevated lactate, hypotonia, and in some patients seizures or myoclonia in individuals from two consanguineous families. A combined respiratory chain deficiency and a defect in mitochondrial protein translation was found. In this study, we report two siblings who are compound heterozygous for the mutations, c.713A>G and c.1003delG, in RMND1. Respiratory chain enzymatic analysis and BN-PAGE showed a combined OXPHOS deficiency. Western blot analysis indicated normal levels of RMND1, but the assembly of the RMND1 homopolymeric complex was highly impaired. The two siblings had a markedly milder phenotype and longer survival compared to previously reported patients. In addition, they had renal failure and hearing impairment. These two newly described patients contribute to delineation of the clinical spectrum associated with RMND1 aberrations.
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Ravn
authors.affiliation: Hans Christian Andersen Children's Hospital, Odense, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Neland
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Wibrand
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Duno
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Elsebet
authors.initials: E
authors.lastname: Ostergaard
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D034381:Hearing Loss / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D014176:Protein Biosynthesis; D051437:Renal Insufficiency / Q000235:genetics* / Q000473:pathology; D017386:Sequence Homology, Amino Acid
chemical_list: D018797:Cell Cycle Proteins; C578871:RMND1 protein, human
keywords: RMND1; hearing impairment; mitochondrial disorder; renal failure; whole-exome sequencing