In a female infant who had fatal infantile cytochrome c oxidase deficiency with predominantly cardiac involvement and relative sparing of skeletal muscle (CEMCOX2; 615119), originally reported by Kennaway et al. (1990), Antonicka et al. (2003) identified compound heterozygosity for a 700C-T transition on 1 allele, resulting in an arg217-to-trp (R217W) substitution, and a splice site mutation in intron 3 on the other allele (C447-3G), resulting in deletion of exon 4 (603646.0002). The splicing error introduced a frameshift and a premature stop codon, resulting in an unstable mRNA and, likely, a null allele.
In an infant girl with isolated complex IV deficiency that was more marked in cardiac than skeletal muscle, who died at day 9 of life with encephalopathy, respiratory depression, and marked cardiac hypertrophy, Alfadhel et al. (2011) identified compound heterozygosity for the R217W missense mutation and a nonsense mutation (S151X; 603646.0003) in the COX15 gene.
In a patient with Leigh syndrome due to cytochrome c oxidase deficiency (256000), Oquendo et al. (2004) identified homozygosity for the R217W mutation. Both parents were heterozygous for the mutation. The authors noted the phenotypic variation associated with this mutation.
