Severe lactic acidosis caused by a novel frame-shift mutation in mitochondrial-encoded cytochrome c oxidase subunit II

• Published in: American journal of medical genetics 2001-07, Vol.102 (1), p.95-99
• Main Authors: Wong, Lee-Jun C., Dai, Pu, Tan, Duanjun, Lipson, Mark, Grix, Art, Sifry-Platt, Mara, Gropman, Andrea, Chen, Tian-Jian
• Format: Article
• Language: English
• Subjects: Acidosis, Lactic - genetics; Acidosis, Lactic - pathology; Base Sequence; Biological and medical sciences; complex IV deficiency; COXII mutation; DNA Mutational Analysis; DNA, Mitochondrial - chemistry; DNA, Mitochondrial - genetics; Electron Transport Complex IV - genetics; Errors of metabolism; Family Health; Fatal Outcome; Female; Frameshift Mutation; Humans; Infant, Newborn; Infant, Premature; Male; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; mitochondrial disorder; mtDNA mutation; Pedigree
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/1096-8628(20010722)102:1<95::AID-AJMG1412>3.0.CO;2-U

We report the first frame‐shift truncation mutation in a mitochondrial DNA (mtDNA)‐encoded subunit II of cytochrome c oxidase (COXII). The mutation was identified by temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing in an infant who died at 12 days of age following a course of apnea, bradycardia, and severe lactic acidosis. The patient had a twin brother who died at two days of age of similar course. The mutation, 8042delAT, produced a truncated protein that was 72 amino acids shorter than the wild type protein. The mutant protein, missing one third of the amino acid residues at the C‐terminal essential for hydrophilic interaction with cytochrome c, ligand binding to CuA and Mg, and the formation of proton and water channels, apparently has devastating effects on mitochondrial respiratory function. © 2001 Wiley‐Liss, Inc.