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Updated: Jul 9, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Biallelic variants in the COQ4 gene caused hereditary spastic paraplegia predominant phenotype
Qiao Wei1, Hao Yu1, Pei-Shan Wang1
1Department of Medical Genetics and Center for Rare Diseases, and Department of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Introduction:
Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by progressive degeneration of upper motor neurons. Homozygous or compound heterozygous variants in COQ4 have been reported to cause primary CoQ10 deficiency-7 (COQ10D7), which is a mitochondrial disease.
Aims:
We aimed to screened COQ4 variants in a cohort of HSP patients.
Methods:
A total of 87 genetically unidentified HSP index patients and their available family members were recruited. Whole exome sequencing (WES) was performed in all probands. Functional studies were performed to identify the pathogenicity of those uncertain significance variants.
Results:
In this study, five different COQ4 variants were identified in three Chinese HSP pedigrees and two variants were novel, c.87dupT (p.Arg30*), c.304C>T (p.Arg102Cys). More importantly, we firstly described two early-onset pure HSP caused by COQ4 variants. Functional studies in patient-derived fibroblast lines revealed a reduction cellular CoQ10 levels and the abnormal mitochondrial structure.
Conclusions:
Our findings revealed that bilateral variants in the COQ4 gene caused HSP predominant phenotype, expanding the phenotypic spectrum of the COQ4-related disorders.
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