Figure 1.

Gene Analysis in Families Affected by CYC1 Mutations

(A) Pedigrees of the Lebanese (with P1) and Sri Lankan (with P2) families. Affected individuals (dark symbols) harbor homozygous (−/−) mutations. Unaffected individuals are either heterozygous (−/+) or wild-type (+/+).

(B) Analysis of CYC1 genomic DNA. For P1, a single candidate disease-causing homozygous missense variant in CYC1 was identified by exome sequencing. For P2, who has defective CIII activity, a candidate-gene strategy resulted in sequencing cDNA obtained from total RNA of cultured fibroblasts and revealed a missense mutation (c.643C>T) in CYC1.

(C and D) Cyt c₁ structures (C) and alignment (D).