With over 1,000 nuclear genes that could potentially cause a mitochondrial disorder, the current diagnostic approach requires targeted molecular analysis, guided by a combination of clinical and biochemical features. However, the expanding molecular and clinical spectrum means that this approach does not always yield a result. Here we report the unusual clinical presentation of “Progressive External Ophthalmoplegia (PEO) plus” Leigh syndrome in three children from a consanguineous family where exome sequencing identified mutations in NDUFS8. NDUFS8 is a nuclear-encoded structural core protein of complex I, and mutations are expected to cause infantile onset and severe disease. Our patients had a later onset, milder and a clinically distinct phenotype, and this gene would not normally be considered in this context. Being untargeted to specific genes, whole exome analysis has the potential to re-write the phenotype and reveal an unexpected molecular aetiology, as illustrated by this family.
CITATION STYLE
Marina, A. D., Schara, U., Pyle, A., Möller-Hartmann, C., Holinski-Feder, E., Abicht, A., … Horvath, R. (2013). NDUFS8-related complex i deficiency extends phenotype from “PEO plus” to leigh syndrome. In JIMD Reports (Vol. 10, pp. 17–22). Springer. https://doi.org/10.1007/8904_2012_195
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