Next generation sequencing technologies for a successful diagnosis in a cold case of Leigh syndrome

BMC Neurology
Paolo AretiniMaria Adelaide Caligo

Abstract

Leigh Syndrome (LS, OMIM 256000) is an early-onset, progressive neurodegenerative disorder characterized by broad clinical and genetic heterogeneity; it is the most frequent disorder of mitochondrial energy production in children. LS inheritance is complex because patients may present mutations in mitochondrial DNA (mtDNA) or in nuclear genes, which predominantly encode proteins involved in respiratory chain structure and assembly or in coenzyme Q10 biogenesis. However, during the last 15 years, the discovery of several genetic mutations and improved knowledge of the natural history of LS has significantly increased our understanding of this mitochondrial disorder. Here we describe a 19-year-old male with clinical and neuroimaging LS diagnosed at 3 years of age. Genetic analyses of the whole mtDNA for maternally inherited LS (MILS) and neuropathy ataxia retinitis pigmentosa (NARP) syndrome failed to reveal any pathogenic mutations. Recently, a missense mutation in ECHS1 and a ~ 35 kb deletion in 10q26.3 involving the region including the gene were identified by WES (whole exome sequencing), uncovering the genetic diagnosis clinically hypothesized for 15 years. We also report the long-term follow-up of this patient, showing a co...Continue Reading

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Citations

Jan 17, 2020·FEBS Letters·Harrison James Burgin, Matthew McKenzie
Apr 25, 2020·Annals of Clinical and Translational Neurology·Dario RonchiGiacomo P Comi
Jul 18, 2020·Journal of Inherited Metabolic Disease·Laura Marti-SanchezBelén Pérez-Dueñas
Oct 29, 2020·American Journal of Medical Genetics. Part a·Mariella T SimonJose E Abdenur
May 2, 2021·Annals of Clinical and Translational Neurology·Kristin EngelstadDarryl C De Vivo
Jan 12, 2022·American Journal of Medical Genetics. Part a·Zhihua YangYibing Chen

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Methods Mentioned

BETA
exome sequencing
proton magnetic resonance
biopsy
PCR

Software Mentioned

Integrative Genome Viewer ( IGV
MuPro
Mute
Polyphen2
CeQer
Auto

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