The weight of genotype on the clinical presentation of COQ7-related hereditary motor axonal neuropathy: a case series and literature review
Laura Alonso Matheus Montouro, Amanda Selvátici Santos Dias, Maria da Penha Ananias Morita, Érica Nogueira Coelho, João Aris Kouyoumdjian, Carla Renata Graca, Fábio de Nazaré Oliveira, Pedro Henrique Marte Arruda Sampaio, Charles Marques Lourenço, Eduardo de Paula EstephanAbstract
Pathogenic variants of the COQ7 gene result in a spectrum of neurological diseases, mainly distal hereditary motor neuropathy (dHMN). We herein report cases of dHMN related to biallelic p.Met1? (c.3G > T [NM_016138]). We compare phenotypes among different COQ7variants reported in the literature.
To describe and analyze our case series, review COQ7-related diseases, and compare our case series with the literature reports.
We described 5 dHMN-p.Met1? patients and searched dHMN AND Brazil and COQ7 in the PubMed/MEDLINE, SciELO and Scopus databases. The categorical variables were expressed as absolute frequencies, and they were compared using the Fisher's exact test and odds ratios with 95%CIs; moreover, exploratory multivariate logistic models with penalization were applied to adjust the associations for genotype/geographic origin.
We analyzed four patients with dHMN plus (two with pyramidal syndrome [PS], one with cerebellar ataxia [CA] and PS, and one with cognitive impairment [CI]) and one with pure dHMN. Our search identified 47 cases of COQ7-related disorders, and The p.Met1? variant was more frequent in dHMN (p < 0.001). In exploratory multivariate models adjusting for genotype/geographic origin, the associations observed in the univariate analyses were partially sustained. The p.Met1? variant remained related to earlier age at onset, CI, and proximal lower limb weakness, whereas Brazilian origin continued to show association with cerebellar manifestations. The 95%CIs were wide due to the small sample, and the results should be interpreted as exploratory.
In conclusion, our findings suggest that the p.Met1? variant is associated with selected phenotype, even after adjustment for genotype/geographic origin. Brazilian origin remained independently related to cerebellar involvement, indicating potential modifying factors beyond genotype.