COQ7 splice site variant causing a spastic paraparesis phenotype in siblings

Abstract

The COQ7 gene is one of the causative genes for primary COQ10 deficiency-related disorders. OMIM-related phenotypes include severe encephalo-myo-nephrocardiopathy and distal hereditary motor neuronopathy. In the present study, we performed the exome sequencing analysis on the proband of a single family with two siblings affected by hereditary spastic paraparesis (HSP). Segregation analysis was conducted on the affected siblings and parents using the Sanger sequencing. In silico secondary and tertiary pre-mRNA structure analysis and protein modelling were carried out. Exome sequencing identified a homozygous splice site variant in the COQ7 gene (NM_016138.5: c.367+5G>A) in the proband. Sanger sequencing confirmed the homozygous status in the affected sibling and heterozygous status in both parents, consistent with autosomal recessive inheritance. In silico secondary and tertiary premRNA structure analysis and protein modelling predicted the deleterious nature of the variant. This case highlights a distinct intermediate phenotype of COQ7 related disorders comprising early-onset spastic paraparesis due to a novel splice site variant in the COQ7 gene. This expands the spectrum of clinical manifestations associated with COQ7 deficiency and underscores the importance of considering COQ7 gene mutations in the differential diagnosis of HSP.