Alternative titles; symbols
ORPHA: 1561; DO: 0080359;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q11.2 | ?Mitochondrial complex IV, deficiency, nuclear type 9 | 616500 | Autosomal recessive | 3 | COA5 | 613920 |
A number sign (#) is used with this entry because of evidence that mitochondrial complex IV deficiency nuclear type 9 (MC4DN9) is caused by homozygous mutation in the COA5 gene (613920) on chromosome 2q11. One such family has been reported.
Mitochondrial complex IV deficiency nuclear type 9 (MC4DN9) is an autosomal recessive multisystem metabolic disorder characterized by neonatal hypertrophic cardiomyopathy resulting in death in early infancy. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV (summary by Huigsloot et al., 2011).
For a discussion of genetic heterogeneity of mitochondrial complex IV (cytochrome c oxidase) deficiency, see 220110.
Huigsloot et al. (2011) reported 2 sibs, born of consanguineous Turkish parents, with cytochrome c oxidase deficiency manifest as lethal neonatal hypertrophic cardiomyopathy. The patients died at ages 8 and 10 days. Postmortem examination showed accumulation of lipid droplets in cardiomyocytes and mitochondrial proliferation; however, neither patient had documented functional impairment of brain or skeletal muscle.
The transmission pattern of MC4DN9 in the family reported by Huigsloot et al. (2011) was consistent with autosomal recessive inheritance.
In 2 sibs, born of consanguineous Turkish parents, with MC4DN9, Huigsloot et al. (2011) identified a homozygous mutation in the C2ORF64 (COA5) gene (A53P; 613920.0001). The activity and amount of complex IV were severely reduced in patient fibroblasts and heart muscle, and the complex IV subcomplexes lacked mitochondrial subunits COX1 (516030), COX2 (516040), COX4 (123864), and COX5A (603773). Complementation of patient fibroblasts with wildtype C2ORF64 resulted in normalization of fully assembled complex IV.
Huigsloot, M., Nijtmans, L. G., Szklarczyk, R., Baars, M. J. H., van den Brand, M. A. M., HendriksFranssen, M. G. M., van den Heuvel, L. P., Smeitink, J. A. M., Huynen, M. A., Rodenburg, R. J. T. A mutation in C2orf64 causes impaired cytochrome C oxidase assembly and mitochondrial cardiomyopathy. Am. J. Hum. Genet. 88: 488-493, 2011. [PubMed: 21457908] [Full Text: https://doi.org/10.1016/j.ajhg.2011.03.002]