Amyotrophic lateral sclerosis is a progressive and devasting disease that affects motor neurons (MNs) in the central nervous system and the spinal cord. Most of the patients died within 3–5 years after the onset of symptoms[1]. Approximately 10% of patients with ALS have a family history. Few effective therapies are available, and the scarcity of treatments requires knowledge of the pathophysiology underlying ALS[2]. At least 40 genes have been reported to be associated with the disease, such as C9orf72, SOD1, TARDBP and FUS, and the amounts are still increasing [3]. ALS-associated genes have provided an opportunity to explore different pathways leading to motor neuron degeneration, including abnormal protein aggregation, altered RNA metabolism, autophagy dysfunction, mitochondrial dysfunction, disorders in axonal transport, and so on [4]. Considering that some of the genes share common pathways with others, studying key molecules and genes associated with these pathways may provide new ideas for exploring and expanding the genotypic spectrum of ALS.
Dysfunction of mitochondria in MNs and energy metabolism deficits are commonly seen in ALS [5]. The COQ7 encoding protein, coenzyme Q7, is a respiration diiron hydroxylase that catalyzes the penultimate step in the biosynthesis of coenzyme Q (CoQ), an essential co-factor in mitochondrial respiration. CoQ deficiency caused by the pathogenic mutation of COQ7 may result in the dysfunction of mitochondrial energy metabolism and its downstream consequences [6]. These may suggest an involvement of COQ7 in ALS. In addition, recent studies have identified homozygous or compound heterozygous COQ7 mutations in patients with distal hereditary motor neuropathy (dHMN) [7, 8], hereditary spastic paraplegia (HSP)[9, 10]. dHMN and HSP were reported to share pathological, clinical, and genetic similarities with ALS [11, 12].
Given the pathological findings in ALS and the clinical, genetic overlap between COQ7 mutation-associated diseases and ALS, we wondered whether COQ7 may contribute to ALS pathogenesis. In addition, no studies have investigated their association before. In this study, we sequenced the COQ7 gene in a large Chinese cohort of ALS patients using next-generation sequencing to investigate their association.