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: Michael J Keogh, D Daud, A Pyle, J Duff, H Griffin, L He, C L Alston, H Steele, S Taggart, A P Basu, R W Taylor, R Horvath, V Ramesh, Patrick F Chinnery
• Journal: Neurogenetics (Neurogenetics) Vol. 16 Issue 1 Pg. 65-7 (Jan 2015) ISSN: 1364-6753 [Electronic] United States
• PMID: 25418441 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Munc18 Proteins
• STXBP1 protein, human
• Electron Transport Complex I

Topics

• Brain (physiopathology)
• Child
• Disease Progression
• Electroencephalography
• Electron Transport Complex I (deficiency, genetics)
• Epilepsy (complications, genetics)
• Exome
• Female
• Humans
• Mitochondrial Diseases (complications, genetics)
• Munc18 Proteins (genetics)
• Mutation, Missense
• Parkinsonian Disorders (complications, genetics)
• Phenotype