title: A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion.
abstract: This report describes two brothers, both deceased in infancy, with severe depletion of mitochondrial DNA (mtDNA) in muscle tissue. Both had feeding difficulties, failure to thrive, severe muscular hypotonia and lactic acidosis. One of the boys developed a renal proximal tubulopathy. A novel homozygous c.686 G-->T missense mutation in the RRM2B gene, encoding the p53-inducible ribonucleotide reductase subunit (p53R2), was identified. This is the third report on mutations in RRM2B associated with severe mtDNA depletion, which further highlights the importance of de novo synthesis of deoxyribonucleotides (dNTPs) for mtDNA maintenance.
authors.affiliation: Department of Clinical Chemistry, Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Göteborg, Sweden. gittan.kollberg@gu.se
authors.forename: Gittan
authors.initials: G
authors.lastname: Kollberg
authors.forename: Niklas
authors.initials: N
authors.lastname: Darin
authors.forename: Karin
authors.initials: K
authors.lastname: Benan
authors.forename: Ali-Reza
authors.initials: AR
authors.lastname: Moslemi
authors.forename: Sigurd
authors.initials: S
authors.lastname: Lindal
authors.forename: Már
authors.initials: M
authors.lastname: Tulinius
authors.forename: Anders
authors.initials: A
authors.lastname: Oldfors
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Holme
mesh_terms: D000140:Acidosis, Lactic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D058186:Acute Kidney Injury / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D003854:Deoxyribonucleotides / Q000096:biosynthesis; D015536:Down-Regulation; D017809:Fatal Outcome; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D009123:Muscle Hypotonia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020125:Mutation, Missense / Q000235:genetics*; D012264:Ribonucleotide Reductases / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D018797:Cell Cycle Proteins; D004272:DNA, Mitochondrial; D003854:Deoxyribonucleotides; D005819:Genetic Markers; C405947:RRM2B protein, human; D012264:Ribonucleotide Reductases