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Lookup NU author(s): Ewen Sommerville, Dr Charlotte Alston, Dr Angela Pyle, Dr Langping He, Gavin Falkous, Professor Patrick Chinnery, Professor Bobby McFarlandORCiD, Professor Robert Taylor
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
Author(s): Sommerville EW, Alston CL, Pyle A, He L, Falkous G, Naismith K, Chinnery PF, McFarland R, Taylor RW
Publication type: Article
Publication status: Published
Journal: Neurology Genetics
Year: 2017
Volume: 3
Issue: 5
Print publication date: 01/10/2017
Online publication date: 22/09/2017
Acceptance date: 21/07/2017
Date deposited: 14/11/2017
ISSN (electronic): 2376-7839
Publisher: Wolters Kluwer Health
URL: https://doi.org/10.1212/NXG.0000000000000187
DOI: 10.1212/NXG.0000000000000187
PubMed id: PMC5610040
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