Summary

Hum Mutat. 2013 Mar;34(3):446-52. doi: 10.1002/humu.22257. Epub 2013 Jan 29.

Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation.

Abstract:

Mitochondrial complex III (CIII) deficiency is a relatively rare disease with high clinical and genetic heterogeneity. CIII comprises 11 subunits encoded by one mitochondrial and 10 nuclear genes. Abnormalities of the nuclear genes such as BCS1L and TTC19 encoding mitochondrial assembly factors are well known, but an explanation of the majority of CIII deficiency remains elusive. Here, we report three patients from a consanguineous Mexican family presenting with neonatal onset of hypoglycemia, lactic acidosis, ketosis, and hyperammonemia. We found a homozygous missense mutation in UQCRC2 that encodes mitochondrial ubiquinol-cytochrome c reductase core protein II by whole-exome sequencing combined with linkage analysis. On the basis of structural modeling, the mutation (p.Arg183Trp) was predicted to destabilize the hydrophobic core at the subunit interface of the core protein II homodimer. In vitro studies using fibroblasts from the index patient clearly indicated CIII deficiency, as well as impaired assembly of the supercomplex formed from complexes I, III, and IV. This is the first described human disease caused by a core protein abnormality in mitochondrial CIII.

日本語要旨:

新生児に重篤な乳酸アシドーシスで発症したミトコンドリア病のメキシコ人家系において、エキソーム解析でミトコンドリア複合体Ⅲコアタンパク2の変異を同定し報告した。この報告は複合体IIIコアタンパク異常を証明した最初の報告である。

PMID:  23281071

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