title: NDUFS8-related Complex I Deficiency Extends Phenotype from "PEO Plus" to Leigh Syndrome.
abstract: 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.
authors: Pediatric Neurology, University of Essen, Essen, Germany.
authors: Adela Della
authors: AD
authors: Marina
authors: Ulrike
authors: U
authors: Schara
authors: Angela
authors: A
authors: Pyle
authors: Claudia
authors: C
authors: Möller-Hartmann
authors: Elke
authors: E
authors: Holinski-Feder
authors: Angela
authors: A
authors: Abicht
authors: Birgit
authors: B
authors: Czermin
authors: Hanns
authors: H
authors: Lochmüller
authors: Helen
authors: H
authors: Griffin
authors: Mauro
authors: M
authors: Santibanez-Koref
authors: Patrick F
authors: PF
authors: Chinnery
authors: Rita
authors: R
authors: Horvath