A novel variant m.8561C>T in the overlapping region of MT-ATP6 and MT-ATP8 in a child with early-onset severe neurological signs

Konstantina Fragaki; Annabelle Chaussenot; Valerie Serre; Cecile Acquaviva; Sylvie Bannwarth; Cecile Rouzier; Brigitte Chabrol; Veronique Paquis-Flucklinger

doi:10.1016/j.ymgmr.2019.100543

A novel variant m.8561C>T in the overlapping region of MT-ATP6 and MT-ATP8 in a child with early-onset severe neurological signs

Mol Genet Metab Rep. 2019 Nov 21:21:100543. doi: 10.1016/j.ymgmr.2019.100543. eCollection 2019 Dec.

Authors

Konstantina Fragaki¹, Annabelle Chaussenot¹, Valerie Serre², Cecile Acquaviva³, Sylvie Bannwarth¹, Cecile Rouzier¹, Brigitte Chabrol⁴, Veronique Paquis-Flucklinger¹

Affiliations

¹ Université Côte d'Azur, CHU, Inserm, CNRS, IRCAN, France.
² UMR7592 CNRS, Institut Jacques Monod, Université Paris Diderot, Nice, France.
³ Department of Inborn Errors of Metabolism and Neonatal Screening, Center of Biology and Pathology Est CHU, Lyon Bron, France.
⁴ Department of Neuropediatrics, Timone Hospital, CHU, Marseille, France.

Abstract

Among mitochondrial diseases, isolated complex V (CV) deficiency represents a rare cause of respiratory chain (RC) dysfunction. In mammalian mitochondrial DNA (mtDNA), MT-ATP6 partly overlaps with MT-ATP8 making double mutations possible, yet extremely rarely reported principally in patients with cardiomyopathy. Here, we report a novel m.8561 C>T substitution in the overlapping region of MT-ATP6 and MT-ATP8 in a child with early-onset ataxia, psychomotor delay and microcephaly, enlarging the clinical manifestations spectrum associated with CV deficiency.

Keywords: ADP, adenosine triphosphate; ATP synthase; ATP, adenosine triphosphate; Ataxia; BN-PAGE, Blue Native-PolyAcrylamide Gel Electrophoresis; CV, complex V; MRI, Magnetic resonance imaging; Microcephaly; Mitochondrial disorders; NARP, Neuropathy, Ataxia, Retinitis Pigmentosa; NGS, Next-generation sequencing; OXPHOS, oxidative phosphorylation; PCR, polymerase chain reaction; PVDF, PolyVinyliDene Fluoride; Psychomotor delay; RC, respiratory chain; RFLP, Restriction Fragment Length Polymorphism; WT, wild-type; mtDNA, mitochondrial DNA.