A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion.
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.
Kollberg
Gittan
G
Department of Clinical Chemistry, Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Göteborg, Sweden. gittan.kollberg@gu.se
Darin
Niklas
N
Benan
Karin
K
Moslemi
Ali-Reza
AR
Lindal
Sigurd
S
Tulinius
Már
M
Oldfors
Anders
A
Holme
Elisabeth
E
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
D018797:Cell Cycle Proteins; D004272:DNA, Mitochondrial; D003854:Deoxyribonucleotides; D005819:Genetic Markers; C405947:RRM2B protein, human; D012264:Ribonucleotide Reductases