Whole-Exome Sequencing Study of Fibroblasts Derived From Patients With Cerebellar Ataxia Referred to Investigate CoQ10 Deficiency

Overview

Journal Neurol Genet

Date 2023 Apr 24

PMID 37090936

Authors

Edoardo Monfrini

Alba Pesini

Fabio Biella

Claudia F R Sobreira

Valentina Emmanuele

Gloria Brescia

Luis Carlos Lopez

Saba Tadesse

Michio Hirano

Giacomo P Comi

Catarina Maria Quinzii

Alessio Di Fonzo

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: Coenzyme Q (CoQ)-deficient cerebellar ataxia can be due to pathogenic variants in genes encoding for CoQ biosynthetic proteins or associated with defects in protein unrelated to its biosynthesis. Diagnosis is crucial because patients may respond favorably to CoQ supplementation. The aim of this study was to identify through whole-exome sequencing (WES) the pathogenic variants, and assess CoQ levels, in fibroblasts from patients with undiagnosed cerebellar ataxia referred to investigate CoQ deficiency.

Methods: WES was performed on genomic DNA extracted from 16 patients. Sequencing data were filtered using a virtual panel of genes associated with CoQ deficiency and/or cerebellar ataxia. CoQ levels were measured by high-performance liquid chromatography in 14 patient-derived fibroblasts.

Results: A definite genetic etiology was identified in 8 samples of 16 (diagnostic yield = 50%). The identified genetic causes were pathogenic variants of the genes () (n = 3 samples), (n = 2), (n = 1), (n = 1), and (n = 1). Five novel mutations were found ( n = 3, n = 1, and n = 1). CoQ levels were significantly decreased in 3/14 fibroblast samples (21.4%), 1 carrying compound heterozygous pathogenic variants, 1 harboring a homozygous pathogenic variant, and 1 with an unknown molecular defect.

Discussion: This work confirms the importance of gene mutations as a frequent genetic cause of cerebellar ataxia and CoQ deficiency and suggests mutations as a novel cause of secondary CoQ deficiency.

Citing Articles

The role of CoQ10 in embryonic development.

He X, Chen H, Liao M, Zhao X, Zhang D, Jiang M J Assist Reprod Genet. 2024; 41(3):767-779.

PMID: 38372883 PMC: 10957822. DOI: 10.1007/s10815-024-03052-6.

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