title: A novel de novo STXBP1 mutation is associated with mitochondrial complex I deficiency and late-onset juvenile-onset parkinsonism.
abstract: Mutations in STXBP1 have recently been identified as a cause of infantile epileptic encephalopathy. The underlying mechanism of the disorder remains unclear and, recently, several case reports have described broad and progressive neurological phenotypes in addition to early-onset epilepsy. Herein, we describe a patient with early-onset epilepsy who subsequently developed a progressive neurological phenotype including parkinsonism in her early teens. A de novo mutation in STXBP1 (c.416C>T, p.(Pro139Leu)) was detected with exome sequencing together with profound impairment of complex I of the mitochondrial respiratory chain on muscle biopsy. These findings implicate a secondary impairment of mitochondrial function in the progressive nature of the disease phenotype.
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keogh
authors.forename: D
authors.initials: D
authors.lastname: Daud
authors.forename: A
authors.initials: A
authors.lastname: Pyle
authors.forename: J
authors.initials: J
authors.lastname: Duff
authors.forename: H
authors.initials: H
authors.lastname: Griffin
authors.forename: L
authors.initials: L
authors.lastname: He
authors.forename: C L
authors.initials: CL
authors.lastname: Alston
authors.forename: H
authors.initials: H
authors.lastname: Steele
authors.forename: S
authors.initials: S
authors.lastname: Taggart
authors.forename: A P
authors.initials: AP
authors.lastname: Basu
authors.forename: R W
authors.initials: RW
authors.lastname: Taylor
authors.forename: R
authors.initials: R
authors.lastname: Horvath
authors.forename: V
authors.initials: V
authors.lastname: Ramesh
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D001921:Brain / Q000503:physiopathology; D002648:Child; D018450:Disease Progression; D004569:Electroencephalography; D042967:Electron Transport Complex I / Q000172:deficiency* / Q000235:genetics; D004827:Epilepsy / Q000150:complications / Q000235:genetics*; D059472:Exome; D005260:Female; D006801:Humans; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics*; D051938:Munc18 Proteins / Q000235:genetics*; D020125:Mutation, Missense; D020734:Parkinsonian Disorders / Q000150:complications / Q000235:genetics*; D010641:Phenotype
chemical_list: D051938:Munc18 Proteins; C497937:STXBP1 protein, human; D042967:Electron Transport Complex I