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

TitleDe novo CTBP1 variant is associated with decreased mitochondrial respiratory chain activities.
Publication TypeJournal Article
Year of Publication2017
AuthorsSommerville, EW, Alston, CL, Pyle, A, He, L, Falkous, G, Naismith, K, Chinnery, PF, McFarland, R, Taylor, RW
JournalNeurol Genet
Volume3
Issue5
Paginatione187
Date Published2017 Oct
ISSN2376-7839
Abstract

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.

DOI10.1212/NXG.0000000000000187
Alternate JournalNeurol Genet
Citation Key10.1212/NXG.0000000000000187
PubMed ID28955726
PubMed Central IDPMC5610040