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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2018

Open Access 01-12-2018 | Research article

Targeted next generation sequencing with an extended gene panel does not impact variant detection in mitochondrial diseases

Authors: Morgane Plutino, Annabelle Chaussenot, Cécile Rouzier, Samira Ait-El-Mkadem, Konstantina Fragaki, Véronique Paquis-Flucklinger, Sylvie Bannwarth

Published in: BMC Medical Genetics | Issue 1/2018

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Abstract

Background

Since the advent of next generation sequencing (NGS), several studies have tried to evaluate the relevance of targeted gene panel sequencing and whole exome sequencing for molecular diagnosis of mitochondrial diseases. The comparison between these different strategies is extremely difficult. A recent study analysed a cohort of patients affected by a mitochondrial disease using a NGS approach based on a targeted gene panel including 132 genes. This strategy led to identify the causative mutations in 15.2% of cases. The number of novel genes responsible for respiratory chain deficiency increases very rapidly.

Methods

In order to determine the impact of larger panels used as a first screening strategy on molecular diagnosis success, we analysed a cohort of 80 patients affected by a mitochondrial disease with a first mitochondrial DNA (mtDNA) NGS screening and secondarily a targeted mitochondrial panel of 281 nuclear genes.

Results

Pathogenic mtDNA abnormalities were identified in 4.1% (1/24) of children and 25% (14/56) of adult patients. The remaining 65 patients were analysed with our targeted mitochondrial panel and this approach enabled us to achieve an identification rate of 21.7% (5/23) in children versus 7.1% (3/42) in adults.

Conclusions

Our results confirm that larger gene panels do not improve diagnostic yield of mitochondrial diseases due to (i) their very high genetic heterogeneity, (ii) the ongoing discovery of novel genes and (iii) mutations in genes apparently not related to mitochondrial function that lead to secondary respiratory chain deficiency.
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Metadata
Title
Targeted next generation sequencing with an extended gene panel does not impact variant detection in mitochondrial diseases
Authors
Morgane Plutino
Annabelle Chaussenot
Cécile Rouzier
Samira Ait-El-Mkadem
Konstantina Fragaki
Véronique Paquis-Flucklinger
Sylvie Bannwarth
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2018
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-018-0568-y

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