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. 2000 Nov;67(5):1104-9.
doi: 10.1016/S0002-9297(07)62940-1. Epub 2000 Sep 28.

Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy

I Valnot  1 , S Osmond, N Gigarel, B Mehaye, J Amiel, V Cormier-Daire, A Munnich, J P Bonnefont, P Rustin, A Rötig
Affiliations

Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy

I Valnot et al. Am J Hum Genet. 2000 Nov.

Abstract

Cytochrome c oxidase (COX) catalyzes both electron transfer from cytochrome c to molecular oxygen and the concomitant vectorial proton pumping across the inner mitochondrial membrane. Studying a large family with multiple cases of neonatal ketoacidotic comas and isolated COX deficiency, we have mapped the disease locus to chromosome 17p13.1, in a region encompassing two candidate genes involved in COX assembly-namely, SCO1 and COX10. Mutation screening revealed compound heterozygosity for SCO1 gene mutations in the patients. The mutated allele, inherited from the father, harbored a 2-bp frameshift deletion (DeltaGA; nt 363-364) resulting in both a premature stop codon and a highly unstable mRNA. The maternally inherited mutation (C520T) changed a highly conserved proline into a leucine in the protein (P174L). This proline, adjacent to the CxxxC copper-binding domain of SCO1, is likely to play a crucial role in the tridimentional structure of the domain. Interestingly, the clinical presentation of SCO1-deficient patients markedly differs from that of patients harboring mutations in other COX assembly and/or maturation genes.

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Figures

Figure 1
Figure 1
Pedigree and haplotype analyses. Haplotypes are given for loci D17S938, D17S1852, D17S799, and D17S921 (top to bottom).
Figure 2
Figure 2
Sequence analysis of SCO1. A, Paternally inherited frameshift mutation in exon 2. B, Maternally inherited mutation in exon 3.
Figure 3
Figure 3
Molecular analysis of SCO1 mutations. A, Sequence analysis of cDNA of patient II.1. B, SSCP screening for the paternally inherited frameshift mutation in the family. C, Screening of the maternally inherited mutation (C520T) in exon 3 by XbaI restriction analysis. D, Sequence alignment of the SCO1 protein from patient II.1, from controls, and from nonhuman sources, as well as of human and yeast SCO2 proteins. F = father; M = mother; C = control; ND = nondigested control; MW = molecular weight.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Online Mendelian Inheritance in Man (OMIM), http://www3.ncbi.nlm.nih.gov/Omim/ (for SURF1 mutations [MIM 185620 and MIM 256000], COX10 mutations [MIM 602125], SCO2 mutations [MIM 604272 and MIM 604377], SCO1 [MIM 603644]

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