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. 2018 Apr 7;19(1):57.
doi: 10.1186/s12881-018-0568-y.

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

Morgane Plutino  1 , Annabelle Chaussenot  1 , Cécile Rouzier  1 , Samira Ait-El-Mkadem  1 , Konstantina Fragaki  1 , Véronique Paquis-Flucklinger  2 , Sylvie Bannwarth  3   4
Affiliations

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

Morgane Plutino et al. BMC Med Genet. .

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.

Keywords: Exome; Mitochondrial disorders; Next generation sequencing; Targeted panel.

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Conflict of interest statement

Ethics approval and consent to participate

Informed consent for diagnostic and research studies was obtained for all subjects in accordance with the Declaration of Helsinki protocols and act n°78–17 of 6 january 1978 on information technology, data files and civil liberties. The department of personal data protection officer of Nice teaching hospital (Ref:E.H.V/C.G) has validated the accuracy of the regulation of the personal data. The consent forms are concordant with national ethical guidelines in diagnostic and clinical research provided by the “fondation maladies rares”. When the subject is a minor, permission from the responsible relative replaces that of the participant in accordance with national legislation. Whenever the minor child is in fact able to give a consent, the minor’s consent must be obtained in addition to the consent of the minor’s legal guardian.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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