|Title||De novo CTBP1 variant is associated with decreased mitochondrial respiratory chain activities.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Sommerville, EW, Alston, CL, Pyle, A, He, L, Falkous, G, Naismith, K, Chinnery, PF, McFarland, R, Taylor, RW|
|Date Published||2017 Oct|
OBJECTIVE: To determine the genetic etiology of a young woman presenting an early-onset, progressive neurodegenerative disorder with evidence of decreased mitochondrial complex I and IV activities in skeletal muscle suggestive of a mitochondrial disorder.
METHODS: A case report including diagnostic workup, whole-exome sequencing of the affected patient, filtering, and prioritization of candidate variants assuming a suspected autosomal recessive mitochondrial disorder and segregation studies.
RESULTS: After excluding candidate variants for an autosomal recessive mitochondrial disorder, re-evaluation of rare and novel heterozygous variants identified a recently reported, recurrent pathogenic heterozygous CTBP1 missense change (c.991C>T, p.Arg331Trp), which was confirmed to have arisen de novo.
CONCLUSIONS: We report the fifth known patient harboring a recurrent pathogenic de novo c.991C>T p.(Arg331Trp) CTBP1 variant, who was initially suspected to have an autosomal recessive mitochondrial disorder. Inheritance of suspected early-onset mitochondrial disease could wrongly be assumed to be autosomal recessive. Hence, this warrants continued re-evaluation of rare and novel heterozygous variants in patients with apparently unsolved suspected mitochondrial disease investigated using next-generation sequencing.
|Alternate Journal||Neurol Genet|
|PubMed Central ID||PMC5610040|