Alternative titles; symbols
HGNC Approved Gene Symbol: COX7B
Cytogenetic location: Xq21.1 Genomic coordinates (GRCh38) : X:77,899,468-77,907,376 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| Xq21.1 | Linear skin defects with multiple congenital anomalies 2 | 300887 | X-linked dominant | 3 |
Cytochrome c oxidase (COX), the terminal component of the respiratory chain complex of most aerobic organisms, is composed of 13 subunits in mammals. Three COX subunits are encoded by mitochondrial DNA, and 10, including COX7B, are encoded by nuclear DNA (summary by Sadlock et al., 1993).
By screening a human endothelial cell library with a partial bovine COX VIIb cDNA, Sadlock et al. (1993) isolated a cDNA encoding human COX VIIb. The predicted 80-amino acid human protein contains a 24-amino acid leader sequence. The mature human and bovine COX VIIb polypeptides are 82% identical. Southern blot analysis indicated that the COX VIIb gene is part of a large gene family in the human genome. In a review article, Lenka et al. (1998) noted that the COX VIIb subunit is found in all mammalian tissues.
Gross (2012) mapped the COX7B gene to chromosome Xq21.1 based on an alignment of the COX7B sequence (GenBank AK311879) with the genomic sequence (GRCh37).
In 4 female patients with reticulolinear aplasia cutis congenita associated with microcephaly, facial dysmorphism, and other congenital anomalies (LSDMCA2; 300887), Indrieri et al. (2012) identified heterozygosity for a 1-bp deletion, a splice site mutation, and a nonsense mutation, respectively (300885.0001-300885.0003).
Indrieri et al. (2012) performed morpholino knockdown of cox7b in medaka fish (Oryzias latipes) and observed a dose-dependent phenotype characterized by microcephaly and microphthalmia, as well as severe cardiac defects including failure of heart loop formation and pericardial edema.
In a female patient with reticulolinear congenital skin defects, microcephaly, facial dysmorphism, and short stature (LSDMCA2; 300887), who was originally described by Zvulunov et al. (1998), Indrieri et al. (2012) identified heterozygosity for a de novo 1-bp deletion (196delC) in exon 3 of the COX7B gene, causing a frameshift predicted to result in premature termination (Leu66CysfsTer48) and a mutant protein lacking the domain that interacts with COX subunits COX4 (123864) and COX6C (124090). The mutation was not found in her parents, in 200 ethnically matched controls, or in the dbSNP or NHLBI Exome Variant Server databases.
In a girl with reticulolinear congenital skin defects, microcephaly, facial dysmorphism, short stature, atrial septal defect and ventricular hypertrophy, right diaphragmatic hernia, and agenesis of the left kidney with ureteral duplication of the right kidney (LSDMCA2; 300887), Indrieri et al. (2012) identified heterozygosity for a de novo A-G transition (41-2A-G) in intron 1 of the COX7B gene, predicted to create a novel splice acceptor site 1 base before the wildtype splice site (Val14Glyfs*19). The mutation was not found in her parents or in the dbSNP or NHLBI Exome Variant Server databases. In vitro analysis demonstrated that 90% of mutant transcripts contained an additional guanine at the start of exon 2, causing out-of-frame transcripts predicted to result in premature termination.
In a girl with reticulolinear congenital skin defects of the face and neck, microcephaly, facial dysmorphism, tetralogy of Fallot, and intellectual disability (LSDMCA2; 300887), Indrieri et al. (2012) identified heterozygosity for a 55C-T transition in exon 2 of the COX7B gene, resulting in a gln19-to-ter (Q19X) substitution. The nonsense mutation was also present in heterozygosity in the proband's mother, who was born with reticulolinear congenital skin defects of the face and neck but had no other manifestations and normal cognitive function. The proband's 3 healthy sisters and healthy brother all inherited the wildtype allele from their mother, and the mutation was not found in the dbSNP or NHLBI Exome Variant Server databases.
Gross, M. B. Personal Communication. Baltimore, Md. 11/8/2012.
Indrieri, A., van Rahden, V. A., Tiranti, V., Morleo, M., Iaconis, D., Tammaro, R., D'Amato, I., Conte, I., Maystadt, I., Demuth, S., Zvulunov, A., Kutsche, K., Zeviani, M., Franco, B. Mutations in COX7B cause microphthalmia with linear skin lesions, and unconventional mitochondrial disease. Am. J. Hum. Genet. 91: 942-949, 2012. [PubMed: 23122588] [Full Text: https://doi.org/10.1016/j.ajhg.2012.09.016]
Lenka, N., Vijayasarathy, C., Mullick, J., Avadhani, N. G. Structural organization and transcription regulation of nuclear genes encoding the mammalian cytochrome c oxidase complex. Prog. Nucleic Acid Res. Molec. Biol. 61: 309-344, 1998. [PubMed: 9752724] [Full Text: https://doi.org/10.1016/s0079-6603(08)60830-2]
Sadlock, J. E., Lightowlers, R. N., Capaldi, R. A., Schon, E. A. Isolation of a cDNA specifying subunit VIIb of human cytochrome c oxidase. Biochim. Biophys. Acta 1172: 223-225, 1993. [PubMed: 8382530] [Full Text: https://doi.org/10.1016/0167-4781(93)90301-s]
Zvulunov, A., Kachko, L., Manor, E., Shinwell, E., Carmi, R. Reticulolinear aplasia cutis congenita of the face and neck: a distinctive cutaneous manifestation in several syndromes linked to Xp22. Brit. J. Derm. 138: 1046-1052, 1998. [PubMed: 9747372] [Full Text: https://doi.org/10.1046/j.1365-2133.1998.02277.x]