Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Sep;134(9):981-91.
doi: 10.1007/s00439-015-1577-y. Epub 2015 Jun 23.

Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome

Martine Tetreault  1 , Somayyeh Fahiminiya, Hana Antonicka, Grant A Mitchell, Michael T Geraghty, Matthew Lines, Kym M Boycott, Eric A Shoubridge, John J Mitchell; Care4Rare Canada Consortium; Jacques L Michaud, Jacek Majewski
Affiliations

Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome

Martine Tetreault et al. Hum Genet. 2015 Sep.

Abstract

Leigh syndrome (LS) is a rare heterogeneous progressive neurodegenerative disorder usually presenting in infancy or early childhood. Clinical presentation is variable and includes psychomotor delay or regression, acute neurological or acidotic episodes, hypotonia, ataxia, spasticity, movement disorders, and corresponding anomalies of the basal ganglia and brain stem on magnetic resonance imaging. To date, 35 genes have been associated with LS, mostly involved in mitochondrial respiratory chain function and encoded in either nuclear or mitochondrial DNA. We used whole-exome sequencing to identify disease-causing variants in four patients with basal ganglia abnormalities and clinical presentations consistent with LS. Compound heterozygote variants in ECHS1, encoding the enzyme enoyl-CoA hydratase were identified. One missense variant (p.Thr180Ala) was common to all four patients and the haplotype surrounding this variant was also shared, suggesting a common ancestor of French-Canadian origin. Rare mutations in ECHS1 as well as in HIBCH, the enzyme downstream in the valine degradation pathway, have been associated with LS or LS-like disorders. A clear clinical overlap is observed between our patients and the reported cases with ECHS1 or HIBCH deficiency. The main clinical features observed in our cohort are T2-hyperintense signal in the globus pallidus and putamen, failure to thrive, developmental delay or regression, and nystagmus. Respiratory chain studies are not strikingly abnormal in our patients: one patient had a mild reduction of complex I and III and another of complex IV. The identification of four additional patients with mutations in ECHS1 highlights the emerging importance of this pathway in LS.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Am J Med Genet A. 2014 Dec;164A(12):3162-9 - PubMed
    1. Brain. 2014 Nov;137(Pt 11):2903-8 - PubMed
    1. Appl Clin Genet. 2014 Nov 13;7:221-34 - PubMed
    1. Ergeb Inn Med Kinderheilkd. 1970;29:155-219 - PubMed
    1. J Bone Miner Res. 2014 Aug;29(8):1805-14 - PubMed

Publication types

Supplementary concepts

LinkOut - more resources