Alston CL

Chinnery PF

Falkous G

He L

McFarland R

Naismith K

Pyle A

Sommerville EW

Taylor RW

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&gt;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&gt;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

Newcastle University E-Prints

English

De novo CTBP1 variant is associated with decreased mitochondrial respiratory chain activities

De novo CTBP1 variant is associated with decreased mitochondrial respiratory chain activities

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