title: Compound heterozygous RMND1 gene variants associated with chronic kidney disease, dilated cardiomyopathy and neurological involvement: a case report.
abstract: BACKGROUND
  Nuclear gene mutations are being increasingly recognised as causes of mitochondrial disease. The nuclear gene RMND1 has recently been implicated in mitochondrial disease, but the spectrum of pathogenic variants and associated phenotype for this gene, has not been fully elucidated.
  
  
  METHODS
  An 11-month-old boy presented with renal impairment associated with a truncal ataxia, bilateral sensorineural hearing loss, hypotonia, delayed visual maturation and global developmental delay. Over a 9-year period, he progressed to chronic kidney disease stage V and developed a dilated cardiomyopathy. Abnormalities in renal and muscle biopsy as well as cytochrome c oxidase activity prompted genetic testing. After exclusion of mitochondrial DNA defects, nuclear genetic studies identified compound heterozygous RMND1 (c.713A>G, p. Asn238Ser and c.565C>T, p.Gln189*) variants.
  
  
  CONCLUSIONS
  We report RMND1 gene variants associated with end stage renal failure, dilated cardiomyopathy, deafness and neurological involvement due to mitochondrial disease. This case expands current knowledge of mitochondrial disease secondary to mutation of the RMND1 gene by further delineating renal manifestations including histopathology. To our knowledge dilated cardiomyopathy has not been reported with renal failure in mitochondrial disease due to mutations of RMND1. The presence of this complication was important in this case as it precluded renal transplantation.
authors.affiliation: Birmingham Childrens Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK.
authors.forename: Asheeta
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Birmingham Childrens Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK.
authors.forename: Isabel
authors.initials: I
authors.lastname: Colmenero
authors.affiliation: Clinical Genetics Unit, West Midlands Regional Genetics Service, Birmingham Women's Hospital, Birmingham, B15 2TG, UK.|Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, OX3 0BP, UK.
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Ragge
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Blakely
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Langping
authors.initials: L
authors.lastname: He
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.affiliation: Clinical Genetics Unit, West Midlands Regional Genetics Service, Birmingham Women's Hospital, Birmingham, B15 2TG, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Vogt
authors.affiliation: Birmingham Childrens Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK. David.Milford@bch.nhs.uk.
authors.forename: David V
authors.initials: DV
authors.lastname: Milford
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D028361:Mitochondrial Diseases / Q000150:complications / Q000378:metabolism*; D009154:Mutation; D009422:Nervous System Diseases / Q000150:complications / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D045222:Electron Transport Chain Complex Proteins; D009687:Nuclear Proteins; C578871:RMND1 protein, human
keywords: Chronic kidney disease; Global developmental delay; Mitochondrial disease; RMND1 gene; Sensorineural hearing loss